Cancer

Colorectal cancer (CRC) in the United States continues to move in two different directions — decreasing in older adults and rising in younger adults, especially in those aged 20-49 years, according to the latest statistics from the American Cancer Society (ACS).

The ACS report, published online earlier this month, revealed that CRC incidence rates declined by 2.5% annually in adults aged ≥ 65 years but increased by 3% annually in adults aged 20-49 between 2013 and 2022 — higher than earlier estimates of 1% to 2% annual increases.

The trends are “concerning” and a “stark reminder that we’re seeing a shifting epidemiology,” said Folasade (Fola) May, MD, PhD, MPhil, director of the gastroenterology quality improvement program at UCLA Health in Los Angeles, who wasn’t involved in the analysis.

The report highlights the need for better education and symptom awareness — including bleeding, iron deficiency symptoms, and changes in bowel habits — among patients and doctors, who may not routinely consider cancer in younger adults, May explained.

“Because so many of the young people diagnosed present with advanced stage disease, early workup is critical to saving lives,” she said.

Rapidly Changing Landscape

In the United States, CRC is the third-most commonly diagnosed cancer in both men and women. CRC is also the second-leading cause of cancer-related deaths and the leading cause in adults aged < 50 years.

“After decades of progress, the risk of dying from colorectal cancer is climbing in younger generations of men and women, confirming a real uptick in disease because of something we’re doing or some other exposure,” Rebecca Siegel, MPH, senior scientific director of surveillance research at ACS and lead author of the report, said in a statement.

For the latest CRC statistics report, ACS scientists analyzed population-based registries, including the National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) program, and mortality data from the CDC’s National Center for Health Statistics.

The report estimated that 158,850 new CRC cases will be diagnosed in the US in 2026, including 108,860 colon cancers and 49,990 rectal cancers; an estimated 55,230 people will die from the disease.

Overall, CRC incidence declined by 0.9% annually from 2013 to 2022, driven by decreases of 2.5% per year in adults aged ≥ 65 years. During the same period, however, incidence rates rose by about 3% per year in adults aged 20-49 years and by 0.4% per year in those aged 50-64 years. CRC mortality also continued to trend downward in adults aged ≥ 65 years by > 2% per year, but mortality increased by 1% per year in adults aged < 50 years since 2004 and in adults aged 50-64 years since 2019.

Nearly half of new CRC cases (45%) now occur in adults aged < 65 years, up from 27% in 1995, illustrating a major shift toward younger age groups, the authors said. Half of early-onset cases occur in people aged 45-49 years who are now eligible for screening, and 3 of 4 early-onset CRC cases are diagnosed at an advanced stage, including about 27% with distant metastases.

“This is partly because of less screening, but it also reflects diagnostic delays,” according to Siegel and coauthors, who noted data show screening uptake remains low in individuals aged 45-49 (37%) and 50-54 (55%) years. The incidence of early-onset CRC increased across all racial and ethnic groups in the US, from 2% annually in Black individuals to 4% annually in Hispanic individuals between 2013 and 2022.

Aside from early-onset trends, the analysis found that tumor location trends shifted as well. Rectal cancer incidence increased in all ages combined (by 1% per year from 2018 to 2022), reversing decades of decline and now accounting for nearly one third of all CRC, compared with 27% in the mid-2000s.

The report also indicated that racial and ethnic disparities persist. Alaska Native individuals had the highest CRC incidence (80.9 per 100,000) and mortality (31.5 per 100,000) in the US, more than twofold that of White patients (35.2 and 12.9 per 100,000, respectively). Asian American, Native Hawaiian, and other Pacific Islanders had the lowest incidence (28.5 per 100,000) and mortality rates (9.2 per 100,000).

Although cancer registries like SEER are not perfect, they are “the best data we have” and overall the SEER data “very reliably represent what is going on in the US population,” May said.

The latest findings also further underscore that CRC is “worsening among younger generations and highlight the immediate need for eligible adults to begin screening at the recommended age of 45,” William Dahut, MD, ACS chief scientific officer, said in the statement.

The study had no commercial funding. The authors and May reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Colorectal cancer (CRC) in the United States continues to move in two different directions — decreasing in older adults and rising in younger adults, especially in those aged 20-49 years, according to the latest statistics from the American Cancer Society (ACS).

The ACS report, published online earlier this month, revealed that CRC incidence rates declined by 2.5% annually in adults aged ≥ 65 years but increased by 3% annually in adults aged 20-49 between 2013 and 2022 — higher than earlier estimates of 1% to 2% annual increases.

The trends are “concerning” and a “stark reminder that we’re seeing a shifting epidemiology,” said Folasade (Fola) May, MD, PhD, MPhil, director of the gastroenterology quality improvement program at UCLA Health in Los Angeles, who wasn’t involved in the analysis.

The report highlights the need for better education and symptom awareness — including bleeding, iron deficiency symptoms, and changes in bowel habits — among patients and doctors, who may not routinely consider cancer in younger adults, May explained.

“Because so many of the young people diagnosed present with advanced stage disease, early workup is critical to saving lives,” she said.

Rapidly Changing Landscape

In the United States, CRC is the third-most commonly diagnosed cancer in both men and women. CRC is also the second-leading cause of cancer-related deaths and the leading cause in adults aged < 50 years.

“After decades of progress, the risk of dying from colorectal cancer is climbing in younger generations of men and women, confirming a real uptick in disease because of something we’re doing or some other exposure,” Rebecca Siegel, MPH, senior scientific director of surveillance research at ACS and lead author of the report, said in a statement.

For the latest CRC statistics report, ACS scientists analyzed population-based registries, including the National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) program, and mortality data from the CDC’s National Center for Health Statistics.

The report estimated that 158,850 new CRC cases will be diagnosed in the US in 2026, including 108,860 colon cancers and 49,990 rectal cancers; an estimated 55,230 people will die from the disease.

Overall, CRC incidence declined by 0.9% annually from 2013 to 2022, driven by decreases of 2.5% per year in adults aged ≥ 65 years. During the same period, however, incidence rates rose by about 3% per year in adults aged 20-49 years and by 0.4% per year in those aged 50-64 years. CRC mortality also continued to trend downward in adults aged ≥ 65 years by > 2% per year, but mortality increased by 1% per year in adults aged < 50 years since 2004 and in adults aged 50-64 years since 2019.

Nearly half of new CRC cases (45%) now occur in adults aged < 65 years, up from 27% in 1995, illustrating a major shift toward younger age groups, the authors said. Half of early-onset cases occur in people aged 45-49 years who are now eligible for screening, and 3 of 4 early-onset CRC cases are diagnosed at an advanced stage, including about 27% with distant metastases.

“This is partly because of less screening, but it also reflects diagnostic delays,” according to Siegel and coauthors, who noted data show screening uptake remains low in individuals aged 45-49 (37%) and 50-54 (55%) years. The incidence of early-onset CRC increased across all racial and ethnic groups in the US, from 2% annually in Black individuals to 4% annually in Hispanic individuals between 2013 and 2022.

Aside from early-onset trends, the analysis found that tumor location trends shifted as well. Rectal cancer incidence increased in all ages combined (by 1% per year from 2018 to 2022), reversing decades of decline and now accounting for nearly one third of all CRC, compared with 27% in the mid-2000s.

The report also indicated that racial and ethnic disparities persist. Alaska Native individuals had the highest CRC incidence (80.9 per 100,000) and mortality (31.5 per 100,000) in the US, more than twofold that of White patients (35.2 and 12.9 per 100,000, respectively). Asian American, Native Hawaiian, and other Pacific Islanders had the lowest incidence (28.5 per 100,000) and mortality rates (9.2 per 100,000).

Although cancer registries like SEER are not perfect, they are “the best data we have” and overall the SEER data “very reliably represent what is going on in the US population,” May said.

The latest findings also further underscore that CRC is “worsening among younger generations and highlight the immediate need for eligible adults to begin screening at the recommended age of 45,” William Dahut, MD, ACS chief scientific officer, said in the statement.

The study had no commercial funding. The authors and May reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Colorectal cancer (CRC) in the United States continues to move in two different directions — decreasing in older adults and rising in younger adults, especially in those aged 20-49 years, according to the latest statistics from the American Cancer Society (ACS).

The ACS report, published online earlier this month, revealed that CRC incidence rates declined by 2.5% annually in adults aged ≥ 65 years but increased by 3% annually in adults aged 20-49 between 2013 and 2022 — higher than earlier estimates of 1% to 2% annual increases.

The trends are “concerning” and a “stark reminder that we’re seeing a shifting epidemiology,” said Folasade (Fola) May, MD, PhD, MPhil, director of the gastroenterology quality improvement program at UCLA Health in Los Angeles, who wasn’t involved in the analysis.

The report highlights the need for better education and symptom awareness — including bleeding, iron deficiency symptoms, and changes in bowel habits — among patients and doctors, who may not routinely consider cancer in younger adults, May explained.

“Because so many of the young people diagnosed present with advanced stage disease, early workup is critical to saving lives,” she said.

Rapidly Changing Landscape

In the United States, CRC is the third-most commonly diagnosed cancer in both men and women. CRC is also the second-leading cause of cancer-related deaths and the leading cause in adults aged < 50 years.

“After decades of progress, the risk of dying from colorectal cancer is climbing in younger generations of men and women, confirming a real uptick in disease because of something we’re doing or some other exposure,” Rebecca Siegel, MPH, senior scientific director of surveillance research at ACS and lead author of the report, said in a statement.

For the latest CRC statistics report, ACS scientists analyzed population-based registries, including the National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) program, and mortality data from the CDC’s National Center for Health Statistics.

The report estimated that 158,850 new CRC cases will be diagnosed in the US in 2026, including 108,860 colon cancers and 49,990 rectal cancers; an estimated 55,230 people will die from the disease.

Overall, CRC incidence declined by 0.9% annually from 2013 to 2022, driven by decreases of 2.5% per year in adults aged ≥ 65 years. During the same period, however, incidence rates rose by about 3% per year in adults aged 20-49 years and by 0.4% per year in those aged 50-64 years. CRC mortality also continued to trend downward in adults aged ≥ 65 years by > 2% per year, but mortality increased by 1% per year in adults aged < 50 years since 2004 and in adults aged 50-64 years since 2019.

Nearly half of new CRC cases (45%) now occur in adults aged < 65 years, up from 27% in 1995, illustrating a major shift toward younger age groups, the authors said. Half of early-onset cases occur in people aged 45-49 years who are now eligible for screening, and 3 of 4 early-onset CRC cases are diagnosed at an advanced stage, including about 27% with distant metastases.

“This is partly because of less screening, but it also reflects diagnostic delays,” according to Siegel and coauthors, who noted data show screening uptake remains low in individuals aged 45-49 (37%) and 50-54 (55%) years. The incidence of early-onset CRC increased across all racial and ethnic groups in the US, from 2% annually in Black individuals to 4% annually in Hispanic individuals between 2013 and 2022.

Aside from early-onset trends, the analysis found that tumor location trends shifted as well. Rectal cancer incidence increased in all ages combined (by 1% per year from 2018 to 2022), reversing decades of decline and now accounting for nearly one third of all CRC, compared with 27% in the mid-2000s.

The report also indicated that racial and ethnic disparities persist. Alaska Native individuals had the highest CRC incidence (80.9 per 100,000) and mortality (31.5 per 100,000) in the US, more than twofold that of White patients (35.2 and 12.9 per 100,000, respectively). Asian American, Native Hawaiian, and other Pacific Islanders had the lowest incidence (28.5 per 100,000) and mortality rates (9.2 per 100,000).

Although cancer registries like SEER are not perfect, they are “the best data we have” and overall the SEER data “very reliably represent what is going on in the US population,” May said.

The latest findings also further underscore that CRC is “worsening among younger generations and highlight the immediate need for eligible adults to begin screening at the recommended age of 45,” William Dahut, MD, ACS chief scientific officer, said in the statement.

The study had no commercial funding. The authors and May reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Anxiety, depression, and suicide rates are elevated for veterans who are survivors of testicular cancer (TC) compared with veterans without cancer, a retrospective analysis finds.

Over 5 years, the cumulative incidence of anxiety and depression was 53.4% in veterans with TC vs 35.0% in matched controls (P < .001; hazard ratio [HR], 1.66), reported Aditya Bagrodia, MD, professor of urology and radiation oncology at the University of California San Diego, et al in Cancer Medicine. The cumulative incidence of suicidality was 5.0% and 0.1%, respectively (P < .001; HR, 22.99).

“More than half of men with testicular cancer contend with these diagnoses,” Bagrodia told Federal Practitioner. “There are risk factors, including chemotherapy, being single or divorced, or unemployed.”

Patients in these groups warrant aggressive screening and intervention, Bagrodia said. TC is the most common cancer in men in the military and the most common malignancy in men aged 18 to 45 years, Bagrodia said: “The vast majority of men who have testicular cancer are curable.”

Patients, however, face an intense burden. 

“One theme that comes up consistently from patients and caregivers is centered around mental health impact, brain fog, anxiety, depression, and difficulty concentrating,” Bagrodia said. “We wanted to dig into this a little bit further. The idea is to shed light on how common these diagnoses are on these young cancer survivors and intervene so we could positively impact their quality of life.”

The study analyzed 2022 patients with TC and 6375 matched controls enrolled at the US Department of Veterans Affairs (VA) from 1990 through 2016. In the cancer cohort, the mean age at diagnosis was 42.46 years, and ages ranged from 18 to 88 years; 89.7% of patients were White, 6.0% were Black, 2.4% were other race, 1.2% were Asian/Pacific Islander, and 0.7% were Native; 6.2% were Hispanic; and 19.9% were diagnosed between 1990 and 1999.

Factors linked to higher rates of anxiety/depression among patients with TC included divorce (HR 1.15, P = .044), unemployment (HR 1.68, P < .001), and receipt of chemotherapy (HR 1.20, P < .001).

The incidence of de novo anxiety/depression was 30.1% for patients with TC vs 16.7% for controls (P < .001), and the incidence of de novo suicidality was 2.4% for patients and 0.1% for controls.

“These are men who are going to beat their cancer and go on to live for decades and decades,” Bagrodia said. “We found that the impact of a diagnosis and chemotherapy can persist beyond the initial time frame.”

It’s not clear, however, why chemotherapy boosts the risk, Bagrodia said. Clinicians who treat patients with TC should let them know that anxiety, depression, and suicidality are common and treatable concerns.

“We've got some wonderful support services, therapy, and medications that can help out with those diagnoses,” Bagrodia said.

The study authors noted limitations such as the retrospective study design and limited consideration of factors that may affect mental health.

“Additionally, the baseline rates of anxiety, depression, and suicidality are high in the VA population, which may limit ability to apply results to the civilian population,” Bagrodia said.

Genitourinary oncologist Philippe Spiess, MD, of Moffitt Cancer Center in Tampa, praised the study in an interview, saying it provides stronger evidence than previous research. 

"It's not only about screening but surveillance, because you never know what kind of challenges they have in their lives,” Spiess told Federal Practitioner, emphasizing the need for clinicians to continue to monitor patients. “They're young, they're vulnerable. Don’t assume they're going to get help somewhere else. You need to be that source that facilitates it.”

No funding is reported. Bagrodia and other authors have no disclosures. Spiess has no disclosures. 

Anxiety, depression, and suicide rates are elevated for veterans who are survivors of testicular cancer (TC) compared with veterans without cancer, a retrospective analysis finds.

Over 5 years, the cumulative incidence of anxiety and depression was 53.4% in veterans with TC vs 35.0% in matched controls (P < .001; hazard ratio [HR], 1.66), reported Aditya Bagrodia, MD, professor of urology and radiation oncology at the University of California San Diego, et al in Cancer Medicine. The cumulative incidence of suicidality was 5.0% and 0.1%, respectively (P < .001; HR, 22.99).

“More than half of men with testicular cancer contend with these diagnoses,” Bagrodia told Federal Practitioner. “There are risk factors, including chemotherapy, being single or divorced, or unemployed.”

Patients in these groups warrant aggressive screening and intervention, Bagrodia said. TC is the most common cancer in men in the military and the most common malignancy in men aged 18 to 45 years, Bagrodia said: “The vast majority of men who have testicular cancer are curable.”

Patients, however, face an intense burden. 

“One theme that comes up consistently from patients and caregivers is centered around mental health impact, brain fog, anxiety, depression, and difficulty concentrating,” Bagrodia said. “We wanted to dig into this a little bit further. The idea is to shed light on how common these diagnoses are on these young cancer survivors and intervene so we could positively impact their quality of life.”

The study analyzed 2022 patients with TC and 6375 matched controls enrolled at the US Department of Veterans Affairs (VA) from 1990 through 2016. In the cancer cohort, the mean age at diagnosis was 42.46 years, and ages ranged from 18 to 88 years; 89.7% of patients were White, 6.0% were Black, 2.4% were other race, 1.2% were Asian/Pacific Islander, and 0.7% were Native; 6.2% were Hispanic; and 19.9% were diagnosed between 1990 and 1999.

Factors linked to higher rates of anxiety/depression among patients with TC included divorce (HR 1.15, P = .044), unemployment (HR 1.68, P < .001), and receipt of chemotherapy (HR 1.20, P < .001).

The incidence of de novo anxiety/depression was 30.1% for patients with TC vs 16.7% for controls (P < .001), and the incidence of de novo suicidality was 2.4% for patients and 0.1% for controls.

“These are men who are going to beat their cancer and go on to live for decades and decades,” Bagrodia said. “We found that the impact of a diagnosis and chemotherapy can persist beyond the initial time frame.”

It’s not clear, however, why chemotherapy boosts the risk, Bagrodia said. Clinicians who treat patients with TC should let them know that anxiety, depression, and suicidality are common and treatable concerns.

“We've got some wonderful support services, therapy, and medications that can help out with those diagnoses,” Bagrodia said.

The study authors noted limitations such as the retrospective study design and limited consideration of factors that may affect mental health.

“Additionally, the baseline rates of anxiety, depression, and suicidality are high in the VA population, which may limit ability to apply results to the civilian population,” Bagrodia said.

Genitourinary oncologist Philippe Spiess, MD, of Moffitt Cancer Center in Tampa, praised the study in an interview, saying it provides stronger evidence than previous research. 

"It's not only about screening but surveillance, because you never know what kind of challenges they have in their lives,” Spiess told Federal Practitioner, emphasizing the need for clinicians to continue to monitor patients. “They're young, they're vulnerable. Don’t assume they're going to get help somewhere else. You need to be that source that facilitates it.”

No funding is reported. Bagrodia and other authors have no disclosures. Spiess has no disclosures. 

Anxiety, depression, and suicide rates are elevated for veterans who are survivors of testicular cancer (TC) compared with veterans without cancer, a retrospective analysis finds.

Over 5 years, the cumulative incidence of anxiety and depression was 53.4% in veterans with TC vs 35.0% in matched controls (P < .001; hazard ratio [HR], 1.66), reported Aditya Bagrodia, MD, professor of urology and radiation oncology at the University of California San Diego, et al in Cancer Medicine. The cumulative incidence of suicidality was 5.0% and 0.1%, respectively (P < .001; HR, 22.99).

“More than half of men with testicular cancer contend with these diagnoses,” Bagrodia told Federal Practitioner. “There are risk factors, including chemotherapy, being single or divorced, or unemployed.”

Patients in these groups warrant aggressive screening and intervention, Bagrodia said. TC is the most common cancer in men in the military and the most common malignancy in men aged 18 to 45 years, Bagrodia said: “The vast majority of men who have testicular cancer are curable.”

Patients, however, face an intense burden. 

“One theme that comes up consistently from patients and caregivers is centered around mental health impact, brain fog, anxiety, depression, and difficulty concentrating,” Bagrodia said. “We wanted to dig into this a little bit further. The idea is to shed light on how common these diagnoses are on these young cancer survivors and intervene so we could positively impact their quality of life.”

The study analyzed 2022 patients with TC and 6375 matched controls enrolled at the US Department of Veterans Affairs (VA) from 1990 through 2016. In the cancer cohort, the mean age at diagnosis was 42.46 years, and ages ranged from 18 to 88 years; 89.7% of patients were White, 6.0% were Black, 2.4% were other race, 1.2% were Asian/Pacific Islander, and 0.7% were Native; 6.2% were Hispanic; and 19.9% were diagnosed between 1990 and 1999.

Factors linked to higher rates of anxiety/depression among patients with TC included divorce (HR 1.15, P = .044), unemployment (HR 1.68, P < .001), and receipt of chemotherapy (HR 1.20, P < .001).

The incidence of de novo anxiety/depression was 30.1% for patients with TC vs 16.7% for controls (P < .001), and the incidence of de novo suicidality was 2.4% for patients and 0.1% for controls.

“These are men who are going to beat their cancer and go on to live for decades and decades,” Bagrodia said. “We found that the impact of a diagnosis and chemotherapy can persist beyond the initial time frame.”

It’s not clear, however, why chemotherapy boosts the risk, Bagrodia said. Clinicians who treat patients with TC should let them know that anxiety, depression, and suicidality are common and treatable concerns.

“We've got some wonderful support services, therapy, and medications that can help out with those diagnoses,” Bagrodia said.

The study authors noted limitations such as the retrospective study design and limited consideration of factors that may affect mental health.

“Additionally, the baseline rates of anxiety, depression, and suicidality are high in the VA population, which may limit ability to apply results to the civilian population,” Bagrodia said.

Genitourinary oncologist Philippe Spiess, MD, of Moffitt Cancer Center in Tampa, praised the study in an interview, saying it provides stronger evidence than previous research. 

"It's not only about screening but surveillance, because you never know what kind of challenges they have in their lives,” Spiess told Federal Practitioner, emphasizing the need for clinicians to continue to monitor patients. “They're young, they're vulnerable. Don’t assume they're going to get help somewhere else. You need to be that source that facilitates it.”

No funding is reported. Bagrodia and other authors have no disclosures. Spiess has no disclosures. 

An international study of nearly 2 million people suggests that meat-free diets can help stave off several major cancers — but it also reached some unexpected conclusions.

In what researchers describe as the largest-ever meta-analysis of meatless diets and cancer risk, compared with meat-eaters, vegetarians showed reduced risks for five cancers, including breast, prostate, and pancreatic. That was independent of factors such as physical activity, body weight, smoking habits, alcohol intake, and medical history.

“This study is really good news for those that follow a vegetarian diet because they have a lower risk of five cancer sites, some of which are really prevalent in the population,” study lead author Yashvee Dunneram, PhD, of Newcastle University, Tyne, England, said at a press briefing on the findings.

The analysis, published in the British Journal of Cancer, looked at data from nine observational studies conducted in the UK, US, India, and Taiwan. In total, they included more than 1.8 million participants who completed detailed questionnaires on lifestyle and medical factors and were followed for a median of 16 years.

While most were omnivores, the population included over 63,000 vegetarians. And compared with their meat-eating counterparts, vegetarians had reduced risks for:

• Multiple myeloma, 31% lower (hazard ratio [HR], 0.69; 95% CI, 0.51-0.93);
• Kidney cancer, 28% lower (HR, 0.72; 95% CI, 0.57-0.92);
• Pancreatic cancer, 21% lower (HR, 0.79; 95% CI, 0.65-0.97);
• Prostate cancer, 12% lower (HR, 0.88; 95% CI, 0.79-0.97); and
• Breast cancer, 9% lower (HR, 0.91; 95% CI, 0.86-0.97).

On the other hand, vegetarians were no less likely to develop colorectal cancer than meat-eaters — which would seem to conflict with a large body of evidence linking high intake of red and processed meats to an increased risk for the disease and consumption of whole grains and fiber to a protective effect.

Dunneram said her team was, in fact, “quite surprised with this finding.”

But the researchers also stressed that the reported intake of processed meats in this global study was low, at a median of about 16 g/d. For comparison, the average intake in the UK general population is more than double that amount.

That point was echoed by Dagfinn Aune, PhD, a researcher at Imperial College London, London, England, who was not involved in the study.

“It’s possible that lumping all meat-eaters (regardless of how much or little meat they ate) together may have diluted any effects of vegetarian diets on cancer risk, particularly if meat intake was low in some studies,” Aune said in comments shared via Science Media Centre.

In another unexpected finding, vegetarians had nearly double the risk for esophageal squamous cell carcinoma compared with meat-eaters.

Senior author Aurora Perez-Cornago, PhD, a nutritional epidemiologist at the University of Oxford, Oxford, England, said she could only speculate on the reasons.

It’s possible, for example, that people who exclude meat from their diets are more likely to have certain nutritional deficiencies. Perez-Cornago noted that low intake of riboflavin (vitamin B2, largely found in meat) has been tied to esophageal cancer risk.

Perhaps most surprising of all, vegans — who eschew all animal products, including dairy foods — had a 40% greater risk for colorectal cancer than meat-eaters (HR, 1.40; 95% CI, 1.12-1.75).

Again, the reasons are unclear, but Dunneram said it could be related to a mineral lacking in some vegans’ diets: calcium. Research has tied higher intake of dairy products, and specifically calcium, to lower colorectal cancer risk.

However, the findings on vegan diets could also come down to numbers, the researchers pointed out: The analysis included 8849 vegans in total and found only 93 cases of colorectal cancer among vegans across seven studies from the US and UK.

Aune said that studies including a “much larger” number of vegans are needed. He also noted that based on prior cohort studies, vegans (and vegetarians) may have a lower overall cancer incidence than meat-eaters.

On balance, the study authors said, meat-free diets may help reduce cancer risk — but vegetarians and vegans might need to boost their intake of certain nutrients, from fortified foods or supplements.

The analysis did have several limitations, according to Anne McTiernan, MD, PhD, a professor at Fred Hutch Cancer Center in Seattle, who studies lifestyle factors and cancer risk.

Besides the relatively small number of vegans, the study lacked data on Black and Hispanic individuals, which limits its generalizability, McTiernan told Medscape Medical News.

And as with any observational research, confounders are an issue. People who follow meat-free diets tend to maintain a lower body weight over time, for example.

Still, McTiernan doubted that body weight fully accounts for the reduced cancer risks seen here as the researchers adjusted for BMI (with weight and height self-reported in some studies and measured in others).

As for the take-home message, McTiernan agreed that vegans, in particular, may want to be careful that they are getting enough of certain vitamins and minerals.

But overall, the findings support the types of plant-rich diets long endorsed by groups such as the World Cancer Research Fund/American Institute for Cancer Research, the experts said.

The analysis also hinted at benefits from cutting out red and processed meat alone.

Among nearly 43,000 pescatarians — people who eat fish but no meat or poultry — the risks for breast (HR, 0.93), colorectal (HR, 0.85), and kidney (HR, 0.73) cancers were reduced relative to meat-eaters. Meanwhile, men who reported eating poultry, but no red or processed meat, had a decreased risk for prostate cancer (HR, 0.93).

In sum, Aune said, “these findings provide further support for dietary recommendations that emphasize higher intakes of whole plant foods, such as whole grains, fruits, vegetables, nuts and legumes and less meat.” And, McTiernan noted, it’s never too late for people to change their dietary habits.

“Clinical trials have shown immediate benefits to vegetarian diets, like reductions in lipids and weight loss — things that can affect health across the board,” she said.

This study was funded by the World Cancer Research Fund, Cancer Research UK, the Medical Research Council and others. The authors declared having no competing interests.

Ernie Mundell is a freelance medical journalist based in Los Angeles. He has more than 30 years of experience, including editorial positions at Reuters Health and HealthDay.

A version of this article first appeared on Medscape.com.

An international study of nearly 2 million people suggests that meat-free diets can help stave off several major cancers — but it also reached some unexpected conclusions.

In what researchers describe as the largest-ever meta-analysis of meatless diets and cancer risk, compared with meat-eaters, vegetarians showed reduced risks for five cancers, including breast, prostate, and pancreatic. That was independent of factors such as physical activity, body weight, smoking habits, alcohol intake, and medical history.

“This study is really good news for those that follow a vegetarian diet because they have a lower risk of five cancer sites, some of which are really prevalent in the population,” study lead author Yashvee Dunneram, PhD, of Newcastle University, Tyne, England, said at a press briefing on the findings.

The analysis, published in the British Journal of Cancer, looked at data from nine observational studies conducted in the UK, US, India, and Taiwan. In total, they included more than 1.8 million participants who completed detailed questionnaires on lifestyle and medical factors and were followed for a median of 16 years.

While most were omnivores, the population included over 63,000 vegetarians. And compared with their meat-eating counterparts, vegetarians had reduced risks for:

• Multiple myeloma, 31% lower (hazard ratio [HR], 0.69; 95% CI, 0.51-0.93);
• Kidney cancer, 28% lower (HR, 0.72; 95% CI, 0.57-0.92);
• Pancreatic cancer, 21% lower (HR, 0.79; 95% CI, 0.65-0.97);
• Prostate cancer, 12% lower (HR, 0.88; 95% CI, 0.79-0.97); and
• Breast cancer, 9% lower (HR, 0.91; 95% CI, 0.86-0.97).

On the other hand, vegetarians were no less likely to develop colorectal cancer than meat-eaters — which would seem to conflict with a large body of evidence linking high intake of red and processed meats to an increased risk for the disease and consumption of whole grains and fiber to a protective effect.

Dunneram said her team was, in fact, “quite surprised with this finding.”

But the researchers also stressed that the reported intake of processed meats in this global study was low, at a median of about 16 g/d. For comparison, the average intake in the UK general population is more than double that amount.

That point was echoed by Dagfinn Aune, PhD, a researcher at Imperial College London, London, England, who was not involved in the study.

“It’s possible that lumping all meat-eaters (regardless of how much or little meat they ate) together may have diluted any effects of vegetarian diets on cancer risk, particularly if meat intake was low in some studies,” Aune said in comments shared via Science Media Centre.

In another unexpected finding, vegetarians had nearly double the risk for esophageal squamous cell carcinoma compared with meat-eaters.

Senior author Aurora Perez-Cornago, PhD, a nutritional epidemiologist at the University of Oxford, Oxford, England, said she could only speculate on the reasons.

It’s possible, for example, that people who exclude meat from their diets are more likely to have certain nutritional deficiencies. Perez-Cornago noted that low intake of riboflavin (vitamin B2, largely found in meat) has been tied to esophageal cancer risk.

Perhaps most surprising of all, vegans — who eschew all animal products, including dairy foods — had a 40% greater risk for colorectal cancer than meat-eaters (HR, 1.40; 95% CI, 1.12-1.75).

Again, the reasons are unclear, but Dunneram said it could be related to a mineral lacking in some vegans’ diets: calcium. Research has tied higher intake of dairy products, and specifically calcium, to lower colorectal cancer risk.

However, the findings on vegan diets could also come down to numbers, the researchers pointed out: The analysis included 8849 vegans in total and found only 93 cases of colorectal cancer among vegans across seven studies from the US and UK.

Aune said that studies including a “much larger” number of vegans are needed. He also noted that based on prior cohort studies, vegans (and vegetarians) may have a lower overall cancer incidence than meat-eaters.

On balance, the study authors said, meat-free diets may help reduce cancer risk — but vegetarians and vegans might need to boost their intake of certain nutrients, from fortified foods or supplements.

The analysis did have several limitations, according to Anne McTiernan, MD, PhD, a professor at Fred Hutch Cancer Center in Seattle, who studies lifestyle factors and cancer risk.

Besides the relatively small number of vegans, the study lacked data on Black and Hispanic individuals, which limits its generalizability, McTiernan told Medscape Medical News.

And as with any observational research, confounders are an issue. People who follow meat-free diets tend to maintain a lower body weight over time, for example.

Still, McTiernan doubted that body weight fully accounts for the reduced cancer risks seen here as the researchers adjusted for BMI (with weight and height self-reported in some studies and measured in others).

As for the take-home message, McTiernan agreed that vegans, in particular, may want to be careful that they are getting enough of certain vitamins and minerals.

But overall, the findings support the types of plant-rich diets long endorsed by groups such as the World Cancer Research Fund/American Institute for Cancer Research, the experts said.

The analysis also hinted at benefits from cutting out red and processed meat alone.

Among nearly 43,000 pescatarians — people who eat fish but no meat or poultry — the risks for breast (HR, 0.93), colorectal (HR, 0.85), and kidney (HR, 0.73) cancers were reduced relative to meat-eaters. Meanwhile, men who reported eating poultry, but no red or processed meat, had a decreased risk for prostate cancer (HR, 0.93).

In sum, Aune said, “these findings provide further support for dietary recommendations that emphasize higher intakes of whole plant foods, such as whole grains, fruits, vegetables, nuts and legumes and less meat.” And, McTiernan noted, it’s never too late for people to change their dietary habits.

“Clinical trials have shown immediate benefits to vegetarian diets, like reductions in lipids and weight loss — things that can affect health across the board,” she said.

This study was funded by the World Cancer Research Fund, Cancer Research UK, the Medical Research Council and others. The authors declared having no competing interests.

Ernie Mundell is a freelance medical journalist based in Los Angeles. He has more than 30 years of experience, including editorial positions at Reuters Health and HealthDay.

A version of this article first appeared on Medscape.com.

An international study of nearly 2 million people suggests that meat-free diets can help stave off several major cancers — but it also reached some unexpected conclusions.

In what researchers describe as the largest-ever meta-analysis of meatless diets and cancer risk, compared with meat-eaters, vegetarians showed reduced risks for five cancers, including breast, prostate, and pancreatic. That was independent of factors such as physical activity, body weight, smoking habits, alcohol intake, and medical history.

“This study is really good news for those that follow a vegetarian diet because they have a lower risk of five cancer sites, some of which are really prevalent in the population,” study lead author Yashvee Dunneram, PhD, of Newcastle University, Tyne, England, said at a press briefing on the findings.

The analysis, published in the British Journal of Cancer, looked at data from nine observational studies conducted in the UK, US, India, and Taiwan. In total, they included more than 1.8 million participants who completed detailed questionnaires on lifestyle and medical factors and were followed for a median of 16 years.

While most were omnivores, the population included over 63,000 vegetarians. And compared with their meat-eating counterparts, vegetarians had reduced risks for:

• Multiple myeloma, 31% lower (hazard ratio [HR], 0.69; 95% CI, 0.51-0.93);
• Kidney cancer, 28% lower (HR, 0.72; 95% CI, 0.57-0.92);
• Pancreatic cancer, 21% lower (HR, 0.79; 95% CI, 0.65-0.97);
• Prostate cancer, 12% lower (HR, 0.88; 95% CI, 0.79-0.97); and
• Breast cancer, 9% lower (HR, 0.91; 95% CI, 0.86-0.97).

On the other hand, vegetarians were no less likely to develop colorectal cancer than meat-eaters — which would seem to conflict with a large body of evidence linking high intake of red and processed meats to an increased risk for the disease and consumption of whole grains and fiber to a protective effect.

Dunneram said her team was, in fact, “quite surprised with this finding.”

But the researchers also stressed that the reported intake of processed meats in this global study was low, at a median of about 16 g/d. For comparison, the average intake in the UK general population is more than double that amount.

That point was echoed by Dagfinn Aune, PhD, a researcher at Imperial College London, London, England, who was not involved in the study.

“It’s possible that lumping all meat-eaters (regardless of how much or little meat they ate) together may have diluted any effects of vegetarian diets on cancer risk, particularly if meat intake was low in some studies,” Aune said in comments shared via Science Media Centre.

In another unexpected finding, vegetarians had nearly double the risk for esophageal squamous cell carcinoma compared with meat-eaters.

Senior author Aurora Perez-Cornago, PhD, a nutritional epidemiologist at the University of Oxford, Oxford, England, said she could only speculate on the reasons.

It’s possible, for example, that people who exclude meat from their diets are more likely to have certain nutritional deficiencies. Perez-Cornago noted that low intake of riboflavin (vitamin B2, largely found in meat) has been tied to esophageal cancer risk.

Perhaps most surprising of all, vegans — who eschew all animal products, including dairy foods — had a 40% greater risk for colorectal cancer than meat-eaters (HR, 1.40; 95% CI, 1.12-1.75).

Again, the reasons are unclear, but Dunneram said it could be related to a mineral lacking in some vegans’ diets: calcium. Research has tied higher intake of dairy products, and specifically calcium, to lower colorectal cancer risk.

However, the findings on vegan diets could also come down to numbers, the researchers pointed out: The analysis included 8849 vegans in total and found only 93 cases of colorectal cancer among vegans across seven studies from the US and UK.

Aune said that studies including a “much larger” number of vegans are needed. He also noted that based on prior cohort studies, vegans (and vegetarians) may have a lower overall cancer incidence than meat-eaters.

On balance, the study authors said, meat-free diets may help reduce cancer risk — but vegetarians and vegans might need to boost their intake of certain nutrients, from fortified foods or supplements.

The analysis did have several limitations, according to Anne McTiernan, MD, PhD, a professor at Fred Hutch Cancer Center in Seattle, who studies lifestyle factors and cancer risk.

Besides the relatively small number of vegans, the study lacked data on Black and Hispanic individuals, which limits its generalizability, McTiernan told Medscape Medical News.

And as with any observational research, confounders are an issue. People who follow meat-free diets tend to maintain a lower body weight over time, for example.

Still, McTiernan doubted that body weight fully accounts for the reduced cancer risks seen here as the researchers adjusted for BMI (with weight and height self-reported in some studies and measured in others).

As for the take-home message, McTiernan agreed that vegans, in particular, may want to be careful that they are getting enough of certain vitamins and minerals.

But overall, the findings support the types of plant-rich diets long endorsed by groups such as the World Cancer Research Fund/American Institute for Cancer Research, the experts said.

The analysis also hinted at benefits from cutting out red and processed meat alone.

Among nearly 43,000 pescatarians — people who eat fish but no meat or poultry — the risks for breast (HR, 0.93), colorectal (HR, 0.85), and kidney (HR, 0.73) cancers were reduced relative to meat-eaters. Meanwhile, men who reported eating poultry, but no red or processed meat, had a decreased risk for prostate cancer (HR, 0.93).

In sum, Aune said, “these findings provide further support for dietary recommendations that emphasize higher intakes of whole plant foods, such as whole grains, fruits, vegetables, nuts and legumes and less meat.” And, McTiernan noted, it’s never too late for people to change their dietary habits.

“Clinical trials have shown immediate benefits to vegetarian diets, like reductions in lipids and weight loss — things that can affect health across the board,” she said.

This study was funded by the World Cancer Research Fund, Cancer Research UK, the Medical Research Council and others. The authors declared having no competing interests.

Ernie Mundell is a freelance medical journalist based in Los Angeles. He has more than 30 years of experience, including editorial positions at Reuters Health and HealthDay.

A version of this article first appeared on Medscape.com.

A trio of new studies, published simultaneously in February in Nature Medicine, add to growing evidence that manipulating the gut microbiome may enhance responses to immunotherapy in selected patients with cancer.

In these small, early-phase studies involving patients with metastatic renal cell carcinoma (RCC), non-small cell lung cancer (NSCLC), and melanoma receiving immune checkpoint inhibitor (ICI) therapy, fecal microbiota transplantation (FMT) was associated with objective response rates that compared favorably with historical or prespecified benchmarks.

The idea that microbiome modulation via FMT “can augment immunotherapy efficacy is probably a good one and these studies certainly support that hypothesis,” said Diwakar Davar, MD, assistant professor of medicine and an oncologist/hematologist at the University of Pittsburgh, Pennsylvania, who wasn’t part of the new work.While “an intriguing approach and certainly worthy of further evaluation,” Davar cautioned that the latest studies are not robust enough to answer the question conclusively.

Although ICIs have improved outcomes for patients with melanoma, NSCLC, and RCC, many patients still do not respond or eventually develop resistance. A growing body of evidence suggests that the gut microbiome can influence the effectiveness of ICI therapy. However, much of this evidence comes from preclinical studies showing that modulating the microbiome via FMT can alter responses to immunotherapy, along with small proof-of-concept human studies — predominantly in melanoma — suggesting this approach may help overcome primary or acquired resistance to anti-PD-1 therapy.

The new studies aimed to build on this foundation by exploring whether FMT could improve ICI responses and clinical outcomes in patients with NSCLC, melanoma, and RCC.

In the phase 2, open-label FMT-LUMINate trial, researchers tested a healthy-donor FMT delivered as oral capsules before patients began immunotherapy. FMT capsules were produced using 80-100 g of feces per dose from screened healthy donors, and patients consumed 30-40 capsules while under supervision. The study included 20 patients with NSCLC and high PD-L1 tumor expression receiving FMT before standard first-line pembrolizumab monotherapy and 20 patients with cutaneous melanoma receiving FMT before ipilimumab plus nivolumab.

In the NSCLC cohort, 16 patients (80%) achieved an objective response. The 80% objective response rate exceeded the prespecified efficacy threshold of 64% and was higher than previously described historical data, which ranged from 39% to 46%, the study team noted.

In the melanoma cohort, FMT before nivolumab and ipilimumab yielded an objective response rate of 75%, also exceeding the historical expected response rates of 50% to 58% among patients receiving this ICI combination.

In patients with NSCLC, no grade 3 or higher adverse events were reported. However, grade 3 or higher adverse events were reported in 13 (65%) patients in the melanoma group, suggesting a potentially accelerated onset of immune-related adverse events. Researchers also observed a higher-than-expected frequency of myocarditis in melanoma patients (15%). These toxicities clustered among patients who had FMT donors enriched in Prevotella spp, highlighting the importance of donor selection for future trials, the researchers explained.

The team plans to assess the potential of FMT to overcome primary resistance to ICI as part of the phase 2 CanBiome2 randomized trial, which aims to enroll 128 patients.

The RCC Data

The other two studies focused on FMT in patients with metastatic RCC. In the phase 1 PERFORM study, 20 treatment-naive patients with metastatic RCC added encapsulated healthy-donor FMT to standard ICI-based regimens — most commonly ipilimumab plus nivolumab, with some patients receiving pembrolizumab plus axitinib or pembrolizumab plus lenvatinib.

The primary endpoint was safety defined by the incidence and severity of immune-related adverse events. The safety endpoint was met; 50% of patients (10 of 20) experienced grade 3 immune-related adverse events, and there were no serious FMT-related toxicities and no grade 4 or 5 events.

Among 18 evaluable patients, nine (50%) achieved an objective response, including two who had complete responses (11%). Notably, most treatment responders did not develop any grade 3 or higher immune-related adverse events, the researchers reported.

Finally, in the phase 2a TACITO trial, 45 patients with treatment-naive metastatic RCC were randomly allocated to receive donor FMT or placebo FMT. Patients received three administrations over 6 months — first via colonoscopy then as capsulized doses, alongside pembrolizumab plus axitinib.

The primary endpoint of 12-month progression-free survival narrowly missed statistical significance — 70% vs 41% (P = .053) — but suggested a benefit in the donor FMT group.

“We need more than 1 year to appreciate statistical significance in terms of progression-free survival,” study investigator Gianluca Ianiro, MD, PhD, with Catholic University of the Sacred Heart, Rome, told Medscape Medical News.

As for secondary endpoints, median progression-free survival was significantly longer with donor FMT (24.0 vs 9.0 months; hazard ratio, 0.50; P = .035) and the objective response rate was higher with donor FMT (52% vs 32%).

Why Might FMT Boost ICI Response?

Conceptually, FMT is intended to reshape the gut ecosystem in ways that favor antitumor immunity, and possibly reduce immune dysregulation.

Across these new studies, the mechanistic story is moving beyond the idea that more diversity is good and toward a model that suggests a benefit to removing or suppressing taxa associated with resistance or inflammatory toxicity.

For example, in the TACITO trial, microbiome analysis confirmed that acquisition or loss of specific bacterial strains was associated with 12-month progression-free survival.

Additionally, results of the FMT-LUMINate trial hinted that the therapeutic benefit of FMT may be driven by eliminating harmful bacteria present at baseline, most notably Enterocloster, Clostridium and Streptococcus spp.

“This bacterial depletion was associated with a favorable immunometabolic milieu,” the FMT-LUMINate researchers wrote. Additionally, the results suggest that “failure to eliminate baseline deleterious taxa may sustain an immunosuppressive metabolic and systemic immune milieu that compromises ICI responses.”

Is FMT Ready for Prime Time?

Ianiro told Medscape Medical News he “definitely” thinks microbiome modulation could eventually become part of standard immunotherapy regimens.

Although the “signal” of benefit is clearly there, Davar cautioned that it’s too early to justify routine, off-trial use of FMT specifically to improve ICI response.

“These remain small, proof-of-concept studies. They are not adequately powered trials of fecal transplants and multiple different covariates haven’t been considered,” Davar said.

The study researchers noted that issues around donor selection and availability, dosing schedules, product standardization, and safety risk stratification need to be resolved.

For example, TACITO’s real-world experience shows logistics can matter. Delays occurred due to capsule unavailability and other scheduling barriers, which led to late dosing and missed or shifted treatments in some patients.

That’s a reminder that scaling FMT for oncology would require robust manufacturing, distribution, and time-sensitive coordination with ICI start dates.

More broadly, “whether FMT is the most suitable method of essentially changing the gut microbiome remains unclear,” explained Davar, who suggested that engineered microbiome therapeutics or tailored therapies may be a preferable, more scalable and tailored long-term solution.

Overall, does this new research provide impetus to develop stool banks? “Probably not,” Davar said.

But is it a call for interested parties to think about clinical trials and experimental products that could influence the gut microbiome? “Those are all probably good ideas,” he said.

The PERFORM, TACITO and FMT-LUMINate trials had no commercial funding. Saman Maleki Vareki, PhD, of the PERFORM trial, is a cofounder of LND Therapeutics Inc and has submitted a US patent application related to FMT donor screening. Ianiro has received personal fees for acting as a speaker for Biocodex and Illumina and for acting as a consultant/advisor for Ferring Therapeutics. Arielle Elkrief, MD, of the FMT-LUMINate trial, has received honoraria from AstraZeneca, Merck, Bristol Myers Squibb, and EMD Serono; consulting fees from EverImmune, NECBio, and Sanofi-Pasteur; and is an inventor on a patent regarding the microbiome and immunotherapy response. Davar had no relevant disclosures.

A version of this article first appeared on Medscape.com.

A trio of new studies, published simultaneously in February in Nature Medicine, add to growing evidence that manipulating the gut microbiome may enhance responses to immunotherapy in selected patients with cancer.

In these small, early-phase studies involving patients with metastatic renal cell carcinoma (RCC), non-small cell lung cancer (NSCLC), and melanoma receiving immune checkpoint inhibitor (ICI) therapy, fecal microbiota transplantation (FMT) was associated with objective response rates that compared favorably with historical or prespecified benchmarks.

The idea that microbiome modulation via FMT “can augment immunotherapy efficacy is probably a good one and these studies certainly support that hypothesis,” said Diwakar Davar, MD, assistant professor of medicine and an oncologist/hematologist at the University of Pittsburgh, Pennsylvania, who wasn’t part of the new work.While “an intriguing approach and certainly worthy of further evaluation,” Davar cautioned that the latest studies are not robust enough to answer the question conclusively.

Although ICIs have improved outcomes for patients with melanoma, NSCLC, and RCC, many patients still do not respond or eventually develop resistance. A growing body of evidence suggests that the gut microbiome can influence the effectiveness of ICI therapy. However, much of this evidence comes from preclinical studies showing that modulating the microbiome via FMT can alter responses to immunotherapy, along with small proof-of-concept human studies — predominantly in melanoma — suggesting this approach may help overcome primary or acquired resistance to anti-PD-1 therapy.

The new studies aimed to build on this foundation by exploring whether FMT could improve ICI responses and clinical outcomes in patients with NSCLC, melanoma, and RCC.

In the phase 2, open-label FMT-LUMINate trial, researchers tested a healthy-donor FMT delivered as oral capsules before patients began immunotherapy. FMT capsules were produced using 80-100 g of feces per dose from screened healthy donors, and patients consumed 30-40 capsules while under supervision. The study included 20 patients with NSCLC and high PD-L1 tumor expression receiving FMT before standard first-line pembrolizumab monotherapy and 20 patients with cutaneous melanoma receiving FMT before ipilimumab plus nivolumab.

In the NSCLC cohort, 16 patients (80%) achieved an objective response. The 80% objective response rate exceeded the prespecified efficacy threshold of 64% and was higher than previously described historical data, which ranged from 39% to 46%, the study team noted.

In the melanoma cohort, FMT before nivolumab and ipilimumab yielded an objective response rate of 75%, also exceeding the historical expected response rates of 50% to 58% among patients receiving this ICI combination.

In patients with NSCLC, no grade 3 or higher adverse events were reported. However, grade 3 or higher adverse events were reported in 13 (65%) patients in the melanoma group, suggesting a potentially accelerated onset of immune-related adverse events. Researchers also observed a higher-than-expected frequency of myocarditis in melanoma patients (15%). These toxicities clustered among patients who had FMT donors enriched in Prevotella spp, highlighting the importance of donor selection for future trials, the researchers explained.

The team plans to assess the potential of FMT to overcome primary resistance to ICI as part of the phase 2 CanBiome2 randomized trial, which aims to enroll 128 patients.

The RCC Data

The other two studies focused on FMT in patients with metastatic RCC. In the phase 1 PERFORM study, 20 treatment-naive patients with metastatic RCC added encapsulated healthy-donor FMT to standard ICI-based regimens — most commonly ipilimumab plus nivolumab, with some patients receiving pembrolizumab plus axitinib or pembrolizumab plus lenvatinib.

The primary endpoint was safety defined by the incidence and severity of immune-related adverse events. The safety endpoint was met; 50% of patients (10 of 20) experienced grade 3 immune-related adverse events, and there were no serious FMT-related toxicities and no grade 4 or 5 events.

Among 18 evaluable patients, nine (50%) achieved an objective response, including two who had complete responses (11%). Notably, most treatment responders did not develop any grade 3 or higher immune-related adverse events, the researchers reported.

Finally, in the phase 2a TACITO trial, 45 patients with treatment-naive metastatic RCC were randomly allocated to receive donor FMT or placebo FMT. Patients received three administrations over 6 months — first via colonoscopy then as capsulized doses, alongside pembrolizumab plus axitinib.

The primary endpoint of 12-month progression-free survival narrowly missed statistical significance — 70% vs 41% (P = .053) — but suggested a benefit in the donor FMT group.

“We need more than 1 year to appreciate statistical significance in terms of progression-free survival,” study investigator Gianluca Ianiro, MD, PhD, with Catholic University of the Sacred Heart, Rome, told Medscape Medical News.

As for secondary endpoints, median progression-free survival was significantly longer with donor FMT (24.0 vs 9.0 months; hazard ratio, 0.50; P = .035) and the objective response rate was higher with donor FMT (52% vs 32%).

Why Might FMT Boost ICI Response?

Conceptually, FMT is intended to reshape the gut ecosystem in ways that favor antitumor immunity, and possibly reduce immune dysregulation.

Across these new studies, the mechanistic story is moving beyond the idea that more diversity is good and toward a model that suggests a benefit to removing or suppressing taxa associated with resistance or inflammatory toxicity.

For example, in the TACITO trial, microbiome analysis confirmed that acquisition or loss of specific bacterial strains was associated with 12-month progression-free survival.

Additionally, results of the FMT-LUMINate trial hinted that the therapeutic benefit of FMT may be driven by eliminating harmful bacteria present at baseline, most notably Enterocloster, Clostridium and Streptococcus spp.

“This bacterial depletion was associated with a favorable immunometabolic milieu,” the FMT-LUMINate researchers wrote. Additionally, the results suggest that “failure to eliminate baseline deleterious taxa may sustain an immunosuppressive metabolic and systemic immune milieu that compromises ICI responses.”

Is FMT Ready for Prime Time?

Ianiro told Medscape Medical News he “definitely” thinks microbiome modulation could eventually become part of standard immunotherapy regimens.

Although the “signal” of benefit is clearly there, Davar cautioned that it’s too early to justify routine, off-trial use of FMT specifically to improve ICI response.

“These remain small, proof-of-concept studies. They are not adequately powered trials of fecal transplants and multiple different covariates haven’t been considered,” Davar said.

The study researchers noted that issues around donor selection and availability, dosing schedules, product standardization, and safety risk stratification need to be resolved.

For example, TACITO’s real-world experience shows logistics can matter. Delays occurred due to capsule unavailability and other scheduling barriers, which led to late dosing and missed or shifted treatments in some patients.

That’s a reminder that scaling FMT for oncology would require robust manufacturing, distribution, and time-sensitive coordination with ICI start dates.

More broadly, “whether FMT is the most suitable method of essentially changing the gut microbiome remains unclear,” explained Davar, who suggested that engineered microbiome therapeutics or tailored therapies may be a preferable, more scalable and tailored long-term solution.

Overall, does this new research provide impetus to develop stool banks? “Probably not,” Davar said.

But is it a call for interested parties to think about clinical trials and experimental products that could influence the gut microbiome? “Those are all probably good ideas,” he said.

The PERFORM, TACITO and FMT-LUMINate trials had no commercial funding. Saman Maleki Vareki, PhD, of the PERFORM trial, is a cofounder of LND Therapeutics Inc and has submitted a US patent application related to FMT donor screening. Ianiro has received personal fees for acting as a speaker for Biocodex and Illumina and for acting as a consultant/advisor for Ferring Therapeutics. Arielle Elkrief, MD, of the FMT-LUMINate trial, has received honoraria from AstraZeneca, Merck, Bristol Myers Squibb, and EMD Serono; consulting fees from EverImmune, NECBio, and Sanofi-Pasteur; and is an inventor on a patent regarding the microbiome and immunotherapy response. Davar had no relevant disclosures.

A version of this article first appeared on Medscape.com.

A trio of new studies, published simultaneously in February in Nature Medicine, add to growing evidence that manipulating the gut microbiome may enhance responses to immunotherapy in selected patients with cancer.

In these small, early-phase studies involving patients with metastatic renal cell carcinoma (RCC), non-small cell lung cancer (NSCLC), and melanoma receiving immune checkpoint inhibitor (ICI) therapy, fecal microbiota transplantation (FMT) was associated with objective response rates that compared favorably with historical or prespecified benchmarks.

The idea that microbiome modulation via FMT “can augment immunotherapy efficacy is probably a good one and these studies certainly support that hypothesis,” said Diwakar Davar, MD, assistant professor of medicine and an oncologist/hematologist at the University of Pittsburgh, Pennsylvania, who wasn’t part of the new work.While “an intriguing approach and certainly worthy of further evaluation,” Davar cautioned that the latest studies are not robust enough to answer the question conclusively.

Although ICIs have improved outcomes for patients with melanoma, NSCLC, and RCC, many patients still do not respond or eventually develop resistance. A growing body of evidence suggests that the gut microbiome can influence the effectiveness of ICI therapy. However, much of this evidence comes from preclinical studies showing that modulating the microbiome via FMT can alter responses to immunotherapy, along with small proof-of-concept human studies — predominantly in melanoma — suggesting this approach may help overcome primary or acquired resistance to anti-PD-1 therapy.

The new studies aimed to build on this foundation by exploring whether FMT could improve ICI responses and clinical outcomes in patients with NSCLC, melanoma, and RCC.

In the phase 2, open-label FMT-LUMINate trial, researchers tested a healthy-donor FMT delivered as oral capsules before patients began immunotherapy. FMT capsules were produced using 80-100 g of feces per dose from screened healthy donors, and patients consumed 30-40 capsules while under supervision. The study included 20 patients with NSCLC and high PD-L1 tumor expression receiving FMT before standard first-line pembrolizumab monotherapy and 20 patients with cutaneous melanoma receiving FMT before ipilimumab plus nivolumab.

In the NSCLC cohort, 16 patients (80%) achieved an objective response. The 80% objective response rate exceeded the prespecified efficacy threshold of 64% and was higher than previously described historical data, which ranged from 39% to 46%, the study team noted.

In the melanoma cohort, FMT before nivolumab and ipilimumab yielded an objective response rate of 75%, also exceeding the historical expected response rates of 50% to 58% among patients receiving this ICI combination.

In patients with NSCLC, no grade 3 or higher adverse events were reported. However, grade 3 or higher adverse events were reported in 13 (65%) patients in the melanoma group, suggesting a potentially accelerated onset of immune-related adverse events. Researchers also observed a higher-than-expected frequency of myocarditis in melanoma patients (15%). These toxicities clustered among patients who had FMT donors enriched in Prevotella spp, highlighting the importance of donor selection for future trials, the researchers explained.

The team plans to assess the potential of FMT to overcome primary resistance to ICI as part of the phase 2 CanBiome2 randomized trial, which aims to enroll 128 patients.

The RCC Data

The other two studies focused on FMT in patients with metastatic RCC. In the phase 1 PERFORM study, 20 treatment-naive patients with metastatic RCC added encapsulated healthy-donor FMT to standard ICI-based regimens — most commonly ipilimumab plus nivolumab, with some patients receiving pembrolizumab plus axitinib or pembrolizumab plus lenvatinib.

The primary endpoint was safety defined by the incidence and severity of immune-related adverse events. The safety endpoint was met; 50% of patients (10 of 20) experienced grade 3 immune-related adverse events, and there were no serious FMT-related toxicities and no grade 4 or 5 events.

Among 18 evaluable patients, nine (50%) achieved an objective response, including two who had complete responses (11%). Notably, most treatment responders did not develop any grade 3 or higher immune-related adverse events, the researchers reported.

Finally, in the phase 2a TACITO trial, 45 patients with treatment-naive metastatic RCC were randomly allocated to receive donor FMT or placebo FMT. Patients received three administrations over 6 months — first via colonoscopy then as capsulized doses, alongside pembrolizumab plus axitinib.

The primary endpoint of 12-month progression-free survival narrowly missed statistical significance — 70% vs 41% (P = .053) — but suggested a benefit in the donor FMT group.

“We need more than 1 year to appreciate statistical significance in terms of progression-free survival,” study investigator Gianluca Ianiro, MD, PhD, with Catholic University of the Sacred Heart, Rome, told Medscape Medical News.

As for secondary endpoints, median progression-free survival was significantly longer with donor FMT (24.0 vs 9.0 months; hazard ratio, 0.50; P = .035) and the objective response rate was higher with donor FMT (52% vs 32%).

Why Might FMT Boost ICI Response?

Conceptually, FMT is intended to reshape the gut ecosystem in ways that favor antitumor immunity, and possibly reduce immune dysregulation.

Across these new studies, the mechanistic story is moving beyond the idea that more diversity is good and toward a model that suggests a benefit to removing or suppressing taxa associated with resistance or inflammatory toxicity.

For example, in the TACITO trial, microbiome analysis confirmed that acquisition or loss of specific bacterial strains was associated with 12-month progression-free survival.

Additionally, results of the FMT-LUMINate trial hinted that the therapeutic benefit of FMT may be driven by eliminating harmful bacteria present at baseline, most notably Enterocloster, Clostridium and Streptococcus spp.

“This bacterial depletion was associated with a favorable immunometabolic milieu,” the FMT-LUMINate researchers wrote. Additionally, the results suggest that “failure to eliminate baseline deleterious taxa may sustain an immunosuppressive metabolic and systemic immune milieu that compromises ICI responses.”

Is FMT Ready for Prime Time?

Ianiro told Medscape Medical News he “definitely” thinks microbiome modulation could eventually become part of standard immunotherapy regimens.

Although the “signal” of benefit is clearly there, Davar cautioned that it’s too early to justify routine, off-trial use of FMT specifically to improve ICI response.

“These remain small, proof-of-concept studies. They are not adequately powered trials of fecal transplants and multiple different covariates haven’t been considered,” Davar said.

The study researchers noted that issues around donor selection and availability, dosing schedules, product standardization, and safety risk stratification need to be resolved.

For example, TACITO’s real-world experience shows logistics can matter. Delays occurred due to capsule unavailability and other scheduling barriers, which led to late dosing and missed or shifted treatments in some patients.

That’s a reminder that scaling FMT for oncology would require robust manufacturing, distribution, and time-sensitive coordination with ICI start dates.

More broadly, “whether FMT is the most suitable method of essentially changing the gut microbiome remains unclear,” explained Davar, who suggested that engineered microbiome therapeutics or tailored therapies may be a preferable, more scalable and tailored long-term solution.

Overall, does this new research provide impetus to develop stool banks? “Probably not,” Davar said.

But is it a call for interested parties to think about clinical trials and experimental products that could influence the gut microbiome? “Those are all probably good ideas,” he said.

The PERFORM, TACITO and FMT-LUMINate trials had no commercial funding. Saman Maleki Vareki, PhD, of the PERFORM trial, is a cofounder of LND Therapeutics Inc and has submitted a US patent application related to FMT donor screening. Ianiro has received personal fees for acting as a speaker for Biocodex and Illumina and for acting as a consultant/advisor for Ferring Therapeutics. Arielle Elkrief, MD, of the FMT-LUMINate trial, has received honoraria from AstraZeneca, Merck, Bristol Myers Squibb, and EMD Serono; consulting fees from EverImmune, NECBio, and Sanofi-Pasteur; and is an inventor on a patent regarding the microbiome and immunotherapy response. Davar had no relevant disclosures.

A version of this article first appeared on Medscape.com.

A pilot program appeared to more than double the rate of germline genetic testing among veterans with metastatic prostate cancer (mPC) by using remote communication rather than relying on clinicians for in-person outreach to patients. 

Of 1952 veterans with mPC, 681 (34.9%) provided consent and 459 (23.5%) completed testing, exceeding the usual 10% to 12% of patients who undergo testing, reported Bruce Montgomery, MD, et al in Cancer.

Although testing is recommended for all patients with mPC to guide therapy and alert relatives who may be at risk, 23.5% is still an impressive number, Montgomery, an oncologist with Veterans Affairs (VA) Puget Sound Health Care System in Seattle told Federal Practitioner: “With a letter and very little money and very little real time from clinicians, we could get testing done at 3 times the rate happening out there in the big wide world,” he said. “For 2000 patients, we needed one research coordinator and a small part of a genetic counselor's time.”

According to the study, germline genetic testing—which examines inherited DNA—is now recommended for all men with mPC by the National Comprehensive Cancer Network, the American Society of Clinical Oncology, and the American Urological Association. Germline genetic testing differs from somatic testing, which seeks genetic changes in the tumors themselves.

In the VA and community at large, the percentage of men with mPC who undergo germline genetic testing is low, Montgomery said. Research suggests < 40% of patients undergo somatic testing.

Germline genetic testing only costs about 10% compared with somatic testing, Montgomery said, and can be conducted at any time. In about 10% of mPC cases, the testing provides insight into the best treatment, he said.

Montgomery noted another benefit to germline genetic testing: It can raise the alarm about pathogenic variants that could boost cancer risk in family members, allowing them to get screened and take action.

There are many reasons veterans do not get tested, Montgomery said. The process is not automatic because patient consent is needed, and clinicians often fail to ask. In some cases, veterans worry about privacy or whether they will lose service-connected benefits if their cancer is blamed on genetics.

The study focused on 2104 veterans with mPC who had already agreed to take part in the Million Veteran Program, a prospective cohort study examining genetic and nongenetic risk for disease. The genetic analysis from that project did not provide guidance about mPC, so researchers approached the veterans directly.

Patients were enrolled from February 2021 to October 2023. A total of 1952 veterans did not opt out when contacted by mail (median age, 75 years; 63% White, 25% Black; 74% urban and 24% rural). The median age of those who consented and completed testing after phone contact was 74 years; 67% of patients were White and 22% were Black; 78% of patients lived in urban communities and 20% lived in rural communities.

Fifty-nine patients (13%) had pathogenic variants, and 37 of those had variants that indicated treatment with targeted therapies. Of the 37, 14 received targeted therapy, 18 were not at the point where targeted therapy was indicated, and 5 were not treated with targeted therapy for various reasons before they died.

Twelve of the 59 patients with pathogenic variants agreed to let the study team contact their first-degree relatives. Thirty relatives underwent testing, and 10 of them were positive for the variants.

Following completion of the study, researchers examined electronic records for the 59 patients with pathogenic variants and found that 19% did not have documentation of the germline finding in the medical record. The authors cited an “urgent need” to standardize where genetic information is included in the records.

While “it seems like a very small number of patients took up testing,” Montgomery said, the study findings are promising: “If we did the same thing nationally in the VA, there would be 15,000 men with metastatic disease, and we’d be testing 5000 of them with almost no effort.”

In an interview, Susan Vadaparampil, PhD, MPH, associate center director of Community Outreach and Engagement at Moffitt Cancer Center, who studies genetic testing, praised the strengths of the study. Vadaparampil, who did not take part in the research, told Federal Practitioner that the study relies on “an intervention that could likely be incorporated into routine clinical practice, a less resource-intensive model that provides posttest counseling for those who test positive, and support to share results with family members.”

However, she said, “testing uptake was uneven based on participant sociodemographic characteristics. It's important to consider how discussions and resources to facilitate testing may need to be adapted to meet the needs of all patients.

“Strategies that facilitate clinicians’ knowledge, comfort, and consistency in discussing testing with all mPC patients are essential,” Vadaparampil added. “Simultaneously using multiple strategies targeted to different levels can further help boost uptake.”

The study was funded by the VA Office of Research and Development, Prostate Cancer Foundation, Pacific Northwest Prostate Cancer SPORE, Institute for Prostate Cancer Research, Congressionally Directed Medical Research Programs (CDMRP), and Put VA Data to Work for Veterans. 

Montgomery discloses relationships with Daiichi Sankyo, INmune Bio, Clovis, Janssen Pharmaceuticals, Johnson and Johnson, and Merck. Some other authors report various disclosures. Vadaparampil has no disclosures.

A pilot program appeared to more than double the rate of germline genetic testing among veterans with metastatic prostate cancer (mPC) by using remote communication rather than relying on clinicians for in-person outreach to patients. 

Of 1952 veterans with mPC, 681 (34.9%) provided consent and 459 (23.5%) completed testing, exceeding the usual 10% to 12% of patients who undergo testing, reported Bruce Montgomery, MD, et al in Cancer.

Although testing is recommended for all patients with mPC to guide therapy and alert relatives who may be at risk, 23.5% is still an impressive number, Montgomery, an oncologist with Veterans Affairs (VA) Puget Sound Health Care System in Seattle told Federal Practitioner: “With a letter and very little money and very little real time from clinicians, we could get testing done at 3 times the rate happening out there in the big wide world,” he said. “For 2000 patients, we needed one research coordinator and a small part of a genetic counselor's time.”

According to the study, germline genetic testing—which examines inherited DNA—is now recommended for all men with mPC by the National Comprehensive Cancer Network, the American Society of Clinical Oncology, and the American Urological Association. Germline genetic testing differs from somatic testing, which seeks genetic changes in the tumors themselves.

In the VA and community at large, the percentage of men with mPC who undergo germline genetic testing is low, Montgomery said. Research suggests < 40% of patients undergo somatic testing.

Germline genetic testing only costs about 10% compared with somatic testing, Montgomery said, and can be conducted at any time. In about 10% of mPC cases, the testing provides insight into the best treatment, he said.

Montgomery noted another benefit to germline genetic testing: It can raise the alarm about pathogenic variants that could boost cancer risk in family members, allowing them to get screened and take action.

There are many reasons veterans do not get tested, Montgomery said. The process is not automatic because patient consent is needed, and clinicians often fail to ask. In some cases, veterans worry about privacy or whether they will lose service-connected benefits if their cancer is blamed on genetics.

The study focused on 2104 veterans with mPC who had already agreed to take part in the Million Veteran Program, a prospective cohort study examining genetic and nongenetic risk for disease. The genetic analysis from that project did not provide guidance about mPC, so researchers approached the veterans directly.

Patients were enrolled from February 2021 to October 2023. A total of 1952 veterans did not opt out when contacted by mail (median age, 75 years; 63% White, 25% Black; 74% urban and 24% rural). The median age of those who consented and completed testing after phone contact was 74 years; 67% of patients were White and 22% were Black; 78% of patients lived in urban communities and 20% lived in rural communities.

Fifty-nine patients (13%) had pathogenic variants, and 37 of those had variants that indicated treatment with targeted therapies. Of the 37, 14 received targeted therapy, 18 were not at the point where targeted therapy was indicated, and 5 were not treated with targeted therapy for various reasons before they died.

Twelve of the 59 patients with pathogenic variants agreed to let the study team contact their first-degree relatives. Thirty relatives underwent testing, and 10 of them were positive for the variants.

Following completion of the study, researchers examined electronic records for the 59 patients with pathogenic variants and found that 19% did not have documentation of the germline finding in the medical record. The authors cited an “urgent need” to standardize where genetic information is included in the records.

While “it seems like a very small number of patients took up testing,” Montgomery said, the study findings are promising: “If we did the same thing nationally in the VA, there would be 15,000 men with metastatic disease, and we’d be testing 5000 of them with almost no effort.”

In an interview, Susan Vadaparampil, PhD, MPH, associate center director of Community Outreach and Engagement at Moffitt Cancer Center, who studies genetic testing, praised the strengths of the study. Vadaparampil, who did not take part in the research, told Federal Practitioner that the study relies on “an intervention that could likely be incorporated into routine clinical practice, a less resource-intensive model that provides posttest counseling for those who test positive, and support to share results with family members.”

However, she said, “testing uptake was uneven based on participant sociodemographic characteristics. It's important to consider how discussions and resources to facilitate testing may need to be adapted to meet the needs of all patients.

“Strategies that facilitate clinicians’ knowledge, comfort, and consistency in discussing testing with all mPC patients are essential,” Vadaparampil added. “Simultaneously using multiple strategies targeted to different levels can further help boost uptake.”

The study was funded by the VA Office of Research and Development, Prostate Cancer Foundation, Pacific Northwest Prostate Cancer SPORE, Institute for Prostate Cancer Research, Congressionally Directed Medical Research Programs (CDMRP), and Put VA Data to Work for Veterans. 

Montgomery discloses relationships with Daiichi Sankyo, INmune Bio, Clovis, Janssen Pharmaceuticals, Johnson and Johnson, and Merck. Some other authors report various disclosures. Vadaparampil has no disclosures.

A pilot program appeared to more than double the rate of germline genetic testing among veterans with metastatic prostate cancer (mPC) by using remote communication rather than relying on clinicians for in-person outreach to patients. 

Of 1952 veterans with mPC, 681 (34.9%) provided consent and 459 (23.5%) completed testing, exceeding the usual 10% to 12% of patients who undergo testing, reported Bruce Montgomery, MD, et al in Cancer.

Although testing is recommended for all patients with mPC to guide therapy and alert relatives who may be at risk, 23.5% is still an impressive number, Montgomery, an oncologist with Veterans Affairs (VA) Puget Sound Health Care System in Seattle told Federal Practitioner: “With a letter and very little money and very little real time from clinicians, we could get testing done at 3 times the rate happening out there in the big wide world,” he said. “For 2000 patients, we needed one research coordinator and a small part of a genetic counselor's time.”

According to the study, germline genetic testing—which examines inherited DNA—is now recommended for all men with mPC by the National Comprehensive Cancer Network, the American Society of Clinical Oncology, and the American Urological Association. Germline genetic testing differs from somatic testing, which seeks genetic changes in the tumors themselves.

In the VA and community at large, the percentage of men with mPC who undergo germline genetic testing is low, Montgomery said. Research suggests < 40% of patients undergo somatic testing.

Germline genetic testing only costs about 10% compared with somatic testing, Montgomery said, and can be conducted at any time. In about 10% of mPC cases, the testing provides insight into the best treatment, he said.

Montgomery noted another benefit to germline genetic testing: It can raise the alarm about pathogenic variants that could boost cancer risk in family members, allowing them to get screened and take action.

There are many reasons veterans do not get tested, Montgomery said. The process is not automatic because patient consent is needed, and clinicians often fail to ask. In some cases, veterans worry about privacy or whether they will lose service-connected benefits if their cancer is blamed on genetics.

The study focused on 2104 veterans with mPC who had already agreed to take part in the Million Veteran Program, a prospective cohort study examining genetic and nongenetic risk for disease. The genetic analysis from that project did not provide guidance about mPC, so researchers approached the veterans directly.

Patients were enrolled from February 2021 to October 2023. A total of 1952 veterans did not opt out when contacted by mail (median age, 75 years; 63% White, 25% Black; 74% urban and 24% rural). The median age of those who consented and completed testing after phone contact was 74 years; 67% of patients were White and 22% were Black; 78% of patients lived in urban communities and 20% lived in rural communities.

Fifty-nine patients (13%) had pathogenic variants, and 37 of those had variants that indicated treatment with targeted therapies. Of the 37, 14 received targeted therapy, 18 were not at the point where targeted therapy was indicated, and 5 were not treated with targeted therapy for various reasons before they died.

Twelve of the 59 patients with pathogenic variants agreed to let the study team contact their first-degree relatives. Thirty relatives underwent testing, and 10 of them were positive for the variants.

Following completion of the study, researchers examined electronic records for the 59 patients with pathogenic variants and found that 19% did not have documentation of the germline finding in the medical record. The authors cited an “urgent need” to standardize where genetic information is included in the records.

While “it seems like a very small number of patients took up testing,” Montgomery said, the study findings are promising: “If we did the same thing nationally in the VA, there would be 15,000 men with metastatic disease, and we’d be testing 5000 of them with almost no effort.”

In an interview, Susan Vadaparampil, PhD, MPH, associate center director of Community Outreach and Engagement at Moffitt Cancer Center, who studies genetic testing, praised the strengths of the study. Vadaparampil, who did not take part in the research, told Federal Practitioner that the study relies on “an intervention that could likely be incorporated into routine clinical practice, a less resource-intensive model that provides posttest counseling for those who test positive, and support to share results with family members.”

However, she said, “testing uptake was uneven based on participant sociodemographic characteristics. It's important to consider how discussions and resources to facilitate testing may need to be adapted to meet the needs of all patients.

“Strategies that facilitate clinicians’ knowledge, comfort, and consistency in discussing testing with all mPC patients are essential,” Vadaparampil added. “Simultaneously using multiple strategies targeted to different levels can further help boost uptake.”

The study was funded by the VA Office of Research and Development, Prostate Cancer Foundation, Pacific Northwest Prostate Cancer SPORE, Institute for Prostate Cancer Research, Congressionally Directed Medical Research Programs (CDMRP), and Put VA Data to Work for Veterans. 

Montgomery discloses relationships with Daiichi Sankyo, INmune Bio, Clovis, Janssen Pharmaceuticals, Johnson and Johnson, and Merck. Some other authors report various disclosures. Vadaparampil has no disclosures.

Patients with advanced cancer treated with immune checkpoint inhibitors appear to have a survival benefit if they receive influenza vaccination, a new retrospective analysis found. The results also suggest no increase in the risk for immune-related adverse events (IRAEs) in these patients and that the improvement in survival outcomes may be stronger among those with cutaneous malignant melanoma.

“Our findings align with a growing body of evidence, mainly from retrospective studies, that suggest a potential association between influenza vaccination during immune checkpoint inhibitor treatment and improved survival among patients with cancer,” wrote senior author Antonis Valachis, MD, PhD, and colleagues in an article published in JCO Clinical Practice on February 9. “An additional clinically relevant observation is that the association between influenza vaccination and survival may vary by tumor type.”

The new research supports “current recommendations to offer influenza vaccination to all patients undergoing cancer therapy, including those receiving the drugs,” Valachis, of the Department of Oncology, Örebro University in Örebro, Sweden, and his coauthors wrote.

“What we observed is that influenza vaccination is safe for patients under immunotherapy treatment,” Valachis told Medscape Medical News. But “whether influenza vaccination can be used to boost immunotherapy effectiveness should be tested in a study with a different design,” such as a prospective interventional trial.

Discussing potential explanations for why influenza vaccination could affect immunotherapy outcomes without affecting rates of IRAEs, Valachis said that this “cannot be answered within the constraints of our study design, since all patients were treated with immunotherapy.”

It may nevertheless be hypothesized that “immune activation triggered by vaccination preferentially stimulates immune mechanisms that enhance immunotherapy efficacy, while sparing those that contribute to IRAEs.”

Steady Was 'Relatively Modestly Sized'

Question marks were raised over the study itself and, as a result, its findings.

Justin Jee, MD, PhD, a thoracic medical oncologist at Memorial Sloan Kettering Cancer Center, New York City, told Medscape Medical News that there are “a lot of challenges when looking at retrospective data.”

“The authors did a very reasonable job of trying to control for confounders and certain time dependent issues, like immortality bias,” he said. “That said, it’s a relatively modestly sized retrospective study for looking at something that has enormous potential for confounding bias that really can’t be captured with any standard statistical method.”

Jee pointed to factors such as providers potentially being more likely to refer people for vaccination if they’re healthier “vs if the patient is in hospice care,” or individuals simply not getting vaccinated because it is not uppermost in their mind.

“Those things are very, very difficult to control for.”

Jee also said he believes the benefit with influenza vaccination being stronger in cutaneous malignant melanoma could be a study artifact, while the lack of difference in rates of IRAEs could be the result of selection bias, but “it’s just impossible to say with a study like this.”

“I’ve seen several studies looking at both COVID and flu vaccines and whether or not they improve immune checkpoint blockade efficacy,” he added, explaining that “some of them say COVID vaccine good, flu vaccine not as good; others say both flu and COVID vaccines good; others say flu vaccine good, COVID vaccine not as good.”

All Patients With Cancer Should Be Vaccinated

What is clear is that “patients with cancer are [at] especially high risk of developing complications from viral illnesses, including flu, including COVID, and vaccines are a very important part of reducing morbidity, mortality, and spread,” Jee said. The “big picture” is that everyone should get the influenza vaccine, especially patients with cancer, “so in that sense I agree with that part of the conclusion of the paper” and that’s “an important message.”

Mini Kamboj, MD, chief medical epidemiologist at Memorial Sloan Kettering Cancer Center, agreed, saying that the results are “consistent with other research showing that vaccines are safe and beneficial for patients on checkpoint inhibitors.”

“While vaccinated patients with melanoma showed the greatest survival benefit, the authors note small sample size and unrecognized differences between the groups as a potential explanation for their findings. This does not change vaccine recommendations as evidence already supports flu vaccine safety and effectiveness in people with lung cancer on checkpoint inhibitors.”

Nearly 600 Patients With Advanced Cancer

The researchers performed a retrospective cohort study of patients from three regions in Sweden who had advanced solid tumors and were treated with PD-1 or PD-L1 inhibitor monotherapy, or PD-1 combination therapy with a cytotoxic T-lymphocyte-associated protein 4 inhibitor, between January 1, 2016, until December 31, 2021. Treatment was given either routinely or as part of a clinical trial.

Electronic medical records were examined to gather data on a range of variables, including age at diagnosis, sex, Charlson Comorbidity Index, type of cancer, primary treatment at diagnosis, number of previous lines of treatment, best treatment response, IRAEs, influenza vaccination status, and date and cause of death.

In all, 587 patients were treated with immune checkpoint inhibition over the study period. They had a median age of 66 years, and 58.1% were men. The most common malignancies were nonsmall cell lung cancer (NSCLC), cutaneous malignant melanoma (32.5%), and renal cell carcinoma (14.7%).

The most commonly used immune checkpoint inhibitor was nivolumab, which was administered to 47.9% of patients, followed by pembrolizumab (34.6%), atezolizumab (9.4%), and nivolumab plus ipilimumab (6.8%).

Only Patients With Malignant Melanoma Benefit

Over the study period, 17.7% of patients underwent influenza vaccination, at a median time between initiation of immune checkpoint inhibition and vaccination of 2 months. Ninety per cent of patients received the vaccine within 9 months of starting treatment.

Time-dependent Cox regression analysis revealed that real-world progression-free survival (rwPFS) was significantly longer with vaccinated patients than unvaccinated patients at a hazard ratio of 0.59 (95% CI, 0.44-0.79), as was overall survival, at a hazard ratio of 0.56 (95% CI, 0.42-0.75).

There was no significant difference in rwPFS and overall survival between vaccinated and unvaccinated patients among those with NSCLC, but significant differences were seen in those with cutaneous malignant melanoma, at hazard ratios of 0.58 (95% CI, 0.36-0.96) and 0.58 (95% CI, 0.36-0.96), respectively.

Restricting the analysis to immune checkpoint inhibitor monotherapy indicated that vaccinated patients had significantly longer rwPFS and overall survival than unvaccinated patients, at hazard ratios of 0.58 (95% CI, 0.43-0.79) and 0.50 (95% CI, 0.38-0.76), respectively.

Finally, the team found that there were no significant differences in the rates of any grade IRAEs between vaccinated and unvaccinated patients, at 48.4% vs 51.2% (P = .455), or in rates of multiple IRAEs, at 15.1% vs 19.2% (P = .297). The therapeutic management and outcomes of IRAEs were also comparable.

No funding or relevant financial relationships were declared.

A version of this article first appeared on Medscape.com.

Patients with advanced cancer treated with immune checkpoint inhibitors appear to have a survival benefit if they receive influenza vaccination, a new retrospective analysis found. The results also suggest no increase in the risk for immune-related adverse events (IRAEs) in these patients and that the improvement in survival outcomes may be stronger among those with cutaneous malignant melanoma.

“Our findings align with a growing body of evidence, mainly from retrospective studies, that suggest a potential association between influenza vaccination during immune checkpoint inhibitor treatment and improved survival among patients with cancer,” wrote senior author Antonis Valachis, MD, PhD, and colleagues in an article published in JCO Clinical Practice on February 9. “An additional clinically relevant observation is that the association between influenza vaccination and survival may vary by tumor type.”

The new research supports “current recommendations to offer influenza vaccination to all patients undergoing cancer therapy, including those receiving the drugs,” Valachis, of the Department of Oncology, Örebro University in Örebro, Sweden, and his coauthors wrote.

“What we observed is that influenza vaccination is safe for patients under immunotherapy treatment,” Valachis told Medscape Medical News. But “whether influenza vaccination can be used to boost immunotherapy effectiveness should be tested in a study with a different design,” such as a prospective interventional trial.

Discussing potential explanations for why influenza vaccination could affect immunotherapy outcomes without affecting rates of IRAEs, Valachis said that this “cannot be answered within the constraints of our study design, since all patients were treated with immunotherapy.”

It may nevertheless be hypothesized that “immune activation triggered by vaccination preferentially stimulates immune mechanisms that enhance immunotherapy efficacy, while sparing those that contribute to IRAEs.”

Steady Was 'Relatively Modestly Sized'

Question marks were raised over the study itself and, as a result, its findings.

Justin Jee, MD, PhD, a thoracic medical oncologist at Memorial Sloan Kettering Cancer Center, New York City, told Medscape Medical News that there are “a lot of challenges when looking at retrospective data.”

“The authors did a very reasonable job of trying to control for confounders and certain time dependent issues, like immortality bias,” he said. “That said, it’s a relatively modestly sized retrospective study for looking at something that has enormous potential for confounding bias that really can’t be captured with any standard statistical method.”

Jee pointed to factors such as providers potentially being more likely to refer people for vaccination if they’re healthier “vs if the patient is in hospice care,” or individuals simply not getting vaccinated because it is not uppermost in their mind.

“Those things are very, very difficult to control for.”

Jee also said he believes the benefit with influenza vaccination being stronger in cutaneous malignant melanoma could be a study artifact, while the lack of difference in rates of IRAEs could be the result of selection bias, but “it’s just impossible to say with a study like this.”

“I’ve seen several studies looking at both COVID and flu vaccines and whether or not they improve immune checkpoint blockade efficacy,” he added, explaining that “some of them say COVID vaccine good, flu vaccine not as good; others say both flu and COVID vaccines good; others say flu vaccine good, COVID vaccine not as good.”

All Patients With Cancer Should Be Vaccinated

What is clear is that “patients with cancer are [at] especially high risk of developing complications from viral illnesses, including flu, including COVID, and vaccines are a very important part of reducing morbidity, mortality, and spread,” Jee said. The “big picture” is that everyone should get the influenza vaccine, especially patients with cancer, “so in that sense I agree with that part of the conclusion of the paper” and that’s “an important message.”

Mini Kamboj, MD, chief medical epidemiologist at Memorial Sloan Kettering Cancer Center, agreed, saying that the results are “consistent with other research showing that vaccines are safe and beneficial for patients on checkpoint inhibitors.”

“While vaccinated patients with melanoma showed the greatest survival benefit, the authors note small sample size and unrecognized differences between the groups as a potential explanation for their findings. This does not change vaccine recommendations as evidence already supports flu vaccine safety and effectiveness in people with lung cancer on checkpoint inhibitors.”

Nearly 600 Patients With Advanced Cancer

The researchers performed a retrospective cohort study of patients from three regions in Sweden who had advanced solid tumors and were treated with PD-1 or PD-L1 inhibitor monotherapy, or PD-1 combination therapy with a cytotoxic T-lymphocyte-associated protein 4 inhibitor, between January 1, 2016, until December 31, 2021. Treatment was given either routinely or as part of a clinical trial.

Electronic medical records were examined to gather data on a range of variables, including age at diagnosis, sex, Charlson Comorbidity Index, type of cancer, primary treatment at diagnosis, number of previous lines of treatment, best treatment response, IRAEs, influenza vaccination status, and date and cause of death.

In all, 587 patients were treated with immune checkpoint inhibition over the study period. They had a median age of 66 years, and 58.1% were men. The most common malignancies were nonsmall cell lung cancer (NSCLC), cutaneous malignant melanoma (32.5%), and renal cell carcinoma (14.7%).

The most commonly used immune checkpoint inhibitor was nivolumab, which was administered to 47.9% of patients, followed by pembrolizumab (34.6%), atezolizumab (9.4%), and nivolumab plus ipilimumab (6.8%).

Only Patients With Malignant Melanoma Benefit

Over the study period, 17.7% of patients underwent influenza vaccination, at a median time between initiation of immune checkpoint inhibition and vaccination of 2 months. Ninety per cent of patients received the vaccine within 9 months of starting treatment.

Time-dependent Cox regression analysis revealed that real-world progression-free survival (rwPFS) was significantly longer with vaccinated patients than unvaccinated patients at a hazard ratio of 0.59 (95% CI, 0.44-0.79), as was overall survival, at a hazard ratio of 0.56 (95% CI, 0.42-0.75).

There was no significant difference in rwPFS and overall survival between vaccinated and unvaccinated patients among those with NSCLC, but significant differences were seen in those with cutaneous malignant melanoma, at hazard ratios of 0.58 (95% CI, 0.36-0.96) and 0.58 (95% CI, 0.36-0.96), respectively.

Restricting the analysis to immune checkpoint inhibitor monotherapy indicated that vaccinated patients had significantly longer rwPFS and overall survival than unvaccinated patients, at hazard ratios of 0.58 (95% CI, 0.43-0.79) and 0.50 (95% CI, 0.38-0.76), respectively.

Finally, the team found that there were no significant differences in the rates of any grade IRAEs between vaccinated and unvaccinated patients, at 48.4% vs 51.2% (P = .455), or in rates of multiple IRAEs, at 15.1% vs 19.2% (P = .297). The therapeutic management and outcomes of IRAEs were also comparable.

No funding or relevant financial relationships were declared.

A version of this article first appeared on Medscape.com.

Patients with advanced cancer treated with immune checkpoint inhibitors appear to have a survival benefit if they receive influenza vaccination, a new retrospective analysis found. The results also suggest no increase in the risk for immune-related adverse events (IRAEs) in these patients and that the improvement in survival outcomes may be stronger among those with cutaneous malignant melanoma.

“Our findings align with a growing body of evidence, mainly from retrospective studies, that suggest a potential association between influenza vaccination during immune checkpoint inhibitor treatment and improved survival among patients with cancer,” wrote senior author Antonis Valachis, MD, PhD, and colleagues in an article published in JCO Clinical Practice on February 9. “An additional clinically relevant observation is that the association between influenza vaccination and survival may vary by tumor type.”

The new research supports “current recommendations to offer influenza vaccination to all patients undergoing cancer therapy, including those receiving the drugs,” Valachis, of the Department of Oncology, Örebro University in Örebro, Sweden, and his coauthors wrote.

“What we observed is that influenza vaccination is safe for patients under immunotherapy treatment,” Valachis told Medscape Medical News. But “whether influenza vaccination can be used to boost immunotherapy effectiveness should be tested in a study with a different design,” such as a prospective interventional trial.

Discussing potential explanations for why influenza vaccination could affect immunotherapy outcomes without affecting rates of IRAEs, Valachis said that this “cannot be answered within the constraints of our study design, since all patients were treated with immunotherapy.”

It may nevertheless be hypothesized that “immune activation triggered by vaccination preferentially stimulates immune mechanisms that enhance immunotherapy efficacy, while sparing those that contribute to IRAEs.”

Steady Was 'Relatively Modestly Sized'

Question marks were raised over the study itself and, as a result, its findings.

Justin Jee, MD, PhD, a thoracic medical oncologist at Memorial Sloan Kettering Cancer Center, New York City, told Medscape Medical News that there are “a lot of challenges when looking at retrospective data.”

“The authors did a very reasonable job of trying to control for confounders and certain time dependent issues, like immortality bias,” he said. “That said, it’s a relatively modestly sized retrospective study for looking at something that has enormous potential for confounding bias that really can’t be captured with any standard statistical method.”

Jee pointed to factors such as providers potentially being more likely to refer people for vaccination if they’re healthier “vs if the patient is in hospice care,” or individuals simply not getting vaccinated because it is not uppermost in their mind.

“Those things are very, very difficult to control for.”

Jee also said he believes the benefit with influenza vaccination being stronger in cutaneous malignant melanoma could be a study artifact, while the lack of difference in rates of IRAEs could be the result of selection bias, but “it’s just impossible to say with a study like this.”

“I’ve seen several studies looking at both COVID and flu vaccines and whether or not they improve immune checkpoint blockade efficacy,” he added, explaining that “some of them say COVID vaccine good, flu vaccine not as good; others say both flu and COVID vaccines good; others say flu vaccine good, COVID vaccine not as good.”

All Patients With Cancer Should Be Vaccinated

What is clear is that “patients with cancer are [at] especially high risk of developing complications from viral illnesses, including flu, including COVID, and vaccines are a very important part of reducing morbidity, mortality, and spread,” Jee said. The “big picture” is that everyone should get the influenza vaccine, especially patients with cancer, “so in that sense I agree with that part of the conclusion of the paper” and that’s “an important message.”

Mini Kamboj, MD, chief medical epidemiologist at Memorial Sloan Kettering Cancer Center, agreed, saying that the results are “consistent with other research showing that vaccines are safe and beneficial for patients on checkpoint inhibitors.”

“While vaccinated patients with melanoma showed the greatest survival benefit, the authors note small sample size and unrecognized differences between the groups as a potential explanation for their findings. This does not change vaccine recommendations as evidence already supports flu vaccine safety and effectiveness in people with lung cancer on checkpoint inhibitors.”

Nearly 600 Patients With Advanced Cancer

The researchers performed a retrospective cohort study of patients from three regions in Sweden who had advanced solid tumors and were treated with PD-1 or PD-L1 inhibitor monotherapy, or PD-1 combination therapy with a cytotoxic T-lymphocyte-associated protein 4 inhibitor, between January 1, 2016, until December 31, 2021. Treatment was given either routinely or as part of a clinical trial.

Electronic medical records were examined to gather data on a range of variables, including age at diagnosis, sex, Charlson Comorbidity Index, type of cancer, primary treatment at diagnosis, number of previous lines of treatment, best treatment response, IRAEs, influenza vaccination status, and date and cause of death.

In all, 587 patients were treated with immune checkpoint inhibition over the study period. They had a median age of 66 years, and 58.1% were men. The most common malignancies were nonsmall cell lung cancer (NSCLC), cutaneous malignant melanoma (32.5%), and renal cell carcinoma (14.7%).

The most commonly used immune checkpoint inhibitor was nivolumab, which was administered to 47.9% of patients, followed by pembrolizumab (34.6%), atezolizumab (9.4%), and nivolumab plus ipilimumab (6.8%).

Only Patients With Malignant Melanoma Benefit

Over the study period, 17.7% of patients underwent influenza vaccination, at a median time between initiation of immune checkpoint inhibition and vaccination of 2 months. Ninety per cent of patients received the vaccine within 9 months of starting treatment.

Time-dependent Cox regression analysis revealed that real-world progression-free survival (rwPFS) was significantly longer with vaccinated patients than unvaccinated patients at a hazard ratio of 0.59 (95% CI, 0.44-0.79), as was overall survival, at a hazard ratio of 0.56 (95% CI, 0.42-0.75).

There was no significant difference in rwPFS and overall survival between vaccinated and unvaccinated patients among those with NSCLC, but significant differences were seen in those with cutaneous malignant melanoma, at hazard ratios of 0.58 (95% CI, 0.36-0.96) and 0.58 (95% CI, 0.36-0.96), respectively.

Restricting the analysis to immune checkpoint inhibitor monotherapy indicated that vaccinated patients had significantly longer rwPFS and overall survival than unvaccinated patients, at hazard ratios of 0.58 (95% CI, 0.43-0.79) and 0.50 (95% CI, 0.38-0.76), respectively.

Finally, the team found that there were no significant differences in the rates of any grade IRAEs between vaccinated and unvaccinated patients, at 48.4% vs 51.2% (P = .455), or in rates of multiple IRAEs, at 15.1% vs 19.2% (P = .297). The therapeutic management and outcomes of IRAEs were also comparable.

No funding or relevant financial relationships were declared.

A version of this article first appeared on Medscape.com.

One of the most common questions my patients ask is, “What diet can help me beat this cancer?” It is a profoundly important question that is worthy of our efforts to answer. In this brief essay, I will take a deep dive into this question in depth and explore the broader clinical and scientific themes it brings into play.

Low-Hanging Fruit: Nutrition Science

A cancer diagnosis can be a deeply disempowering experience. Although I have not lived with cancer myself, I have seen this play out repeatedly over the past 5 years in my role as an oncologist treating patients with hematologic malignancies.

Our diet is an important part of our personal identity, culturally and spiritually. If lifestyle changes, such as a modified diet or more exercise, can contribute to cancer treatment, it may help us regain a sense of control over our lives, one that cancer so often cruelly strips away. I hypothesize that, among other factors, this is why diet is so important to our patients.

Another factor is exposure to a compelling diet-cancer narrative. Nearly every day, a media headline appears claiming that eating a particular food, or drinking coffee, can either increase or decrease your risk for a certain disease.

These claims, however, are often based on studies of large observational datasets where individuals fill out surveys about their dietary habits and are subsequently assessed for disease outcomes. In these studies, people aren’t asked to eat a particular diet; instead, their dietary habits are analyzed by researchers who have endless permutations to explore. This, in a nutshell, is the field of nutritional epidemiology.

In my opinion, nutritional epidemiology represents the collision of the well-intentioned effort to answer clinically meaningful questions with the ease — and near-infinite permutations — of dietary questions that can be asked from an increasingly larger number of different datasets.

Now, factor in the never-ending appetite (pun intended) of journalism and the public’s desire for dietary studies, and you create the perfect storm of incentives that drives a flood of low-quality nutritional science. These studies are highly malleable to analytical choices and can essentially produce results consistent with your prior beliefs, regardless of the philosophical inclination you have (pro keto-diet, pro-vegan, etc.). I love quoting this study to my trainees that, depending on what variables are included and how the analysis is conducted, the same dataset could be used to show that red meat either increases, decreases, or has no effect on all-cause mortality. Unfortunately, much of the evidence base for diet in cancer comes from similarly confounded, low-quality studies.

Diet and Cancer

So, what do randomized trials show for diet and cancer?

The highest-quality evidence is generated from randomized controlled trials. One of their key advantages is the ability to control both measured and unmeasured confounders.

Unfortunately, the evidence supporting diet as an anticancer modality in randomized trials in patients with cancer is bleak. We did a systematic review of all randomized trials of dietary intervention ever done in patients with cancer. Most of the trials measured outcomes such as feasibility (often small pilot studies that measure variables such as weight changes or lab values). The trials that measure clinical endpoints, such as survival, were largely negative and demonstrated no meaningful effect of diet on outcomes. Take trials exploring whether a Mediterranean diet helps prevent breast cancer recurrence, or whether a diet rich in fruits and vegetables improves prostate cancer outcomes. Although these diets may offer benefits, these studies found that specific diets did not change the natural history of cancer.

Myeloma and Diet

In my specialty, multiple myeloma, I am thankful that some trials are beginning to shed light on whether diet influences cancer outcomes.

One study, which was recently published in Cancer Discovery, explored whether a high-fiber, plant-based diet could potentially slow or delay progression from myeloma precursor conditions toward full-blown multiple myeloma. The trial enrolled 23 participants, with the primary endpoints of dietary adherence and changes to BMI. Measures of progression to multiple myeloma were exploratory at best. Yet, the media coverage, as well as the majority of the discussion and results sections of this study manuscript, claimed that the diet changes can prevent progression to myeloma.

However, the study design and conclusions were flawed. The paper focused on two patients who had some improvement in disease trajectory, while descriptions of patients who had an increase in their bone marrow plasma cell percentage were relegated to the supplemental section.

As a primary investigator of a trial in smoldering myeloma where we use advanced imaging as an alternative to pharmacologic treatment, I frequently see myeloma markers fluctuate and often decrease. I attribute these changes to random variation, or possibly regression to the mean, rather than the effect of any intervention.

Future randomized studies by this group used primary endpoints of stool butyrate level and implement dietary interventions for a limited period— 2 weeks in one study and 12 weeks in another — to again assess the impact of a high-fiber, plant-based diet on progression to myeloma. Although there are no data yet, the limited timeframes in these studies severely limits generalizability for outcomes that would truly matter, such as cancer control and longevity. There is also no evidence that changes in stool butyrate levels influence patient outcomes.

High-quality science — whether it is evaluating diet or other interventions—requires high-quality data, effort, funding, and time. It is not impossible.

We can draw inspiration from the CHALLENGE trial. This large, randomized trial, which took over a decade to complete, assessed the benefit of a structured exercise program in the adjuvant setting for colon cancer. The endpoint of this study was disease-free survival, and the intervention was deployed over a much longer period: 3 years, as opposed to a 2-week intervention. This trial took years from inception to completion, but it yielded a conclusive result and will probably lead to more dedicated efforts to facilitate exercise programs for patients with cancer.

Our patients deserve the same effort as the CHALLENGE trial to answer their important dietary questions. Until such trials are completed, we must acknowledge, with humility, that despite the common sense and feel-good factor that many diets offer us, their impact on cancer remains uncertain.

Conversely, we must recognize that even if diet does not cure or alter the course of a certain cancer, it can still impact quality of life, treatment tolerance, and other supportive care outcomes, making it an important factor in patient care.

This is what I tell my patients that it is unlikely any one diet will change the trajectory of your cancer. Focus on eating healthy, and remember that most things in moderation are fine. Your diet remains an important risk factor and determinant for health outcomes beyond cancer. Eat what makes you happy. You are going through a tough time, and this is not the moment to impose stringent restrictions on yourself.

A version of this article first appeared on Medscape.com.

One of the most common questions my patients ask is, “What diet can help me beat this cancer?” It is a profoundly important question that is worthy of our efforts to answer. In this brief essay, I will take a deep dive into this question in depth and explore the broader clinical and scientific themes it brings into play.

Low-Hanging Fruit: Nutrition Science

A cancer diagnosis can be a deeply disempowering experience. Although I have not lived with cancer myself, I have seen this play out repeatedly over the past 5 years in my role as an oncologist treating patients with hematologic malignancies.

Our diet is an important part of our personal identity, culturally and spiritually. If lifestyle changes, such as a modified diet or more exercise, can contribute to cancer treatment, it may help us regain a sense of control over our lives, one that cancer so often cruelly strips away. I hypothesize that, among other factors, this is why diet is so important to our patients.

Another factor is exposure to a compelling diet-cancer narrative. Nearly every day, a media headline appears claiming that eating a particular food, or drinking coffee, can either increase or decrease your risk for a certain disease.

These claims, however, are often based on studies of large observational datasets where individuals fill out surveys about their dietary habits and are subsequently assessed for disease outcomes. In these studies, people aren’t asked to eat a particular diet; instead, their dietary habits are analyzed by researchers who have endless permutations to explore. This, in a nutshell, is the field of nutritional epidemiology.

In my opinion, nutritional epidemiology represents the collision of the well-intentioned effort to answer clinically meaningful questions with the ease — and near-infinite permutations — of dietary questions that can be asked from an increasingly larger number of different datasets.

Now, factor in the never-ending appetite (pun intended) of journalism and the public’s desire for dietary studies, and you create the perfect storm of incentives that drives a flood of low-quality nutritional science. These studies are highly malleable to analytical choices and can essentially produce results consistent with your prior beliefs, regardless of the philosophical inclination you have (pro keto-diet, pro-vegan, etc.). I love quoting this study to my trainees that, depending on what variables are included and how the analysis is conducted, the same dataset could be used to show that red meat either increases, decreases, or has no effect on all-cause mortality. Unfortunately, much of the evidence base for diet in cancer comes from similarly confounded, low-quality studies.

Diet and Cancer

So, what do randomized trials show for diet and cancer?

The highest-quality evidence is generated from randomized controlled trials. One of their key advantages is the ability to control both measured and unmeasured confounders.

Unfortunately, the evidence supporting diet as an anticancer modality in randomized trials in patients with cancer is bleak. We did a systematic review of all randomized trials of dietary intervention ever done in patients with cancer. Most of the trials measured outcomes such as feasibility (often small pilot studies that measure variables such as weight changes or lab values). The trials that measure clinical endpoints, such as survival, were largely negative and demonstrated no meaningful effect of diet on outcomes. Take trials exploring whether a Mediterranean diet helps prevent breast cancer recurrence, or whether a diet rich in fruits and vegetables improves prostate cancer outcomes. Although these diets may offer benefits, these studies found that specific diets did not change the natural history of cancer.

Myeloma and Diet

In my specialty, multiple myeloma, I am thankful that some trials are beginning to shed light on whether diet influences cancer outcomes.

One study, which was recently published in Cancer Discovery, explored whether a high-fiber, plant-based diet could potentially slow or delay progression from myeloma precursor conditions toward full-blown multiple myeloma. The trial enrolled 23 participants, with the primary endpoints of dietary adherence and changes to BMI. Measures of progression to multiple myeloma were exploratory at best. Yet, the media coverage, as well as the majority of the discussion and results sections of this study manuscript, claimed that the diet changes can prevent progression to myeloma.

However, the study design and conclusions were flawed. The paper focused on two patients who had some improvement in disease trajectory, while descriptions of patients who had an increase in their bone marrow plasma cell percentage were relegated to the supplemental section.

As a primary investigator of a trial in smoldering myeloma where we use advanced imaging as an alternative to pharmacologic treatment, I frequently see myeloma markers fluctuate and often decrease. I attribute these changes to random variation, or possibly regression to the mean, rather than the effect of any intervention.

Future randomized studies by this group used primary endpoints of stool butyrate level and implement dietary interventions for a limited period— 2 weeks in one study and 12 weeks in another — to again assess the impact of a high-fiber, plant-based diet on progression to myeloma. Although there are no data yet, the limited timeframes in these studies severely limits generalizability for outcomes that would truly matter, such as cancer control and longevity. There is also no evidence that changes in stool butyrate levels influence patient outcomes.

High-quality science — whether it is evaluating diet or other interventions—requires high-quality data, effort, funding, and time. It is not impossible.

We can draw inspiration from the CHALLENGE trial. This large, randomized trial, which took over a decade to complete, assessed the benefit of a structured exercise program in the adjuvant setting for colon cancer. The endpoint of this study was disease-free survival, and the intervention was deployed over a much longer period: 3 years, as opposed to a 2-week intervention. This trial took years from inception to completion, but it yielded a conclusive result and will probably lead to more dedicated efforts to facilitate exercise programs for patients with cancer.

Our patients deserve the same effort as the CHALLENGE trial to answer their important dietary questions. Until such trials are completed, we must acknowledge, with humility, that despite the common sense and feel-good factor that many diets offer us, their impact on cancer remains uncertain.

Conversely, we must recognize that even if diet does not cure or alter the course of a certain cancer, it can still impact quality of life, treatment tolerance, and other supportive care outcomes, making it an important factor in patient care.

This is what I tell my patients that it is unlikely any one diet will change the trajectory of your cancer. Focus on eating healthy, and remember that most things in moderation are fine. Your diet remains an important risk factor and determinant for health outcomes beyond cancer. Eat what makes you happy. You are going through a tough time, and this is not the moment to impose stringent restrictions on yourself.

A version of this article first appeared on Medscape.com.

One of the most common questions my patients ask is, “What diet can help me beat this cancer?” It is a profoundly important question that is worthy of our efforts to answer. In this brief essay, I will take a deep dive into this question in depth and explore the broader clinical and scientific themes it brings into play.

Low-Hanging Fruit: Nutrition Science

A cancer diagnosis can be a deeply disempowering experience. Although I have not lived with cancer myself, I have seen this play out repeatedly over the past 5 years in my role as an oncologist treating patients with hematologic malignancies.

Our diet is an important part of our personal identity, culturally and spiritually. If lifestyle changes, such as a modified diet or more exercise, can contribute to cancer treatment, it may help us regain a sense of control over our lives, one that cancer so often cruelly strips away. I hypothesize that, among other factors, this is why diet is so important to our patients.

Another factor is exposure to a compelling diet-cancer narrative. Nearly every day, a media headline appears claiming that eating a particular food, or drinking coffee, can either increase or decrease your risk for a certain disease.

These claims, however, are often based on studies of large observational datasets where individuals fill out surveys about their dietary habits and are subsequently assessed for disease outcomes. In these studies, people aren’t asked to eat a particular diet; instead, their dietary habits are analyzed by researchers who have endless permutations to explore. This, in a nutshell, is the field of nutritional epidemiology.

In my opinion, nutritional epidemiology represents the collision of the well-intentioned effort to answer clinically meaningful questions with the ease — and near-infinite permutations — of dietary questions that can be asked from an increasingly larger number of different datasets.

Now, factor in the never-ending appetite (pun intended) of journalism and the public’s desire for dietary studies, and you create the perfect storm of incentives that drives a flood of low-quality nutritional science. These studies are highly malleable to analytical choices and can essentially produce results consistent with your prior beliefs, regardless of the philosophical inclination you have (pro keto-diet, pro-vegan, etc.). I love quoting this study to my trainees that, depending on what variables are included and how the analysis is conducted, the same dataset could be used to show that red meat either increases, decreases, or has no effect on all-cause mortality. Unfortunately, much of the evidence base for diet in cancer comes from similarly confounded, low-quality studies.

Diet and Cancer

So, what do randomized trials show for diet and cancer?

The highest-quality evidence is generated from randomized controlled trials. One of their key advantages is the ability to control both measured and unmeasured confounders.

Unfortunately, the evidence supporting diet as an anticancer modality in randomized trials in patients with cancer is bleak. We did a systematic review of all randomized trials of dietary intervention ever done in patients with cancer. Most of the trials measured outcomes such as feasibility (often small pilot studies that measure variables such as weight changes or lab values). The trials that measure clinical endpoints, such as survival, were largely negative and demonstrated no meaningful effect of diet on outcomes. Take trials exploring whether a Mediterranean diet helps prevent breast cancer recurrence, or whether a diet rich in fruits and vegetables improves prostate cancer outcomes. Although these diets may offer benefits, these studies found that specific diets did not change the natural history of cancer.

Myeloma and Diet

In my specialty, multiple myeloma, I am thankful that some trials are beginning to shed light on whether diet influences cancer outcomes.

One study, which was recently published in Cancer Discovery, explored whether a high-fiber, plant-based diet could potentially slow or delay progression from myeloma precursor conditions toward full-blown multiple myeloma. The trial enrolled 23 participants, with the primary endpoints of dietary adherence and changes to BMI. Measures of progression to multiple myeloma were exploratory at best. Yet, the media coverage, as well as the majority of the discussion and results sections of this study manuscript, claimed that the diet changes can prevent progression to myeloma.

However, the study design and conclusions were flawed. The paper focused on two patients who had some improvement in disease trajectory, while descriptions of patients who had an increase in their bone marrow plasma cell percentage were relegated to the supplemental section.

As a primary investigator of a trial in smoldering myeloma where we use advanced imaging as an alternative to pharmacologic treatment, I frequently see myeloma markers fluctuate and often decrease. I attribute these changes to random variation, or possibly regression to the mean, rather than the effect of any intervention.

Future randomized studies by this group used primary endpoints of stool butyrate level and implement dietary interventions for a limited period— 2 weeks in one study and 12 weeks in another — to again assess the impact of a high-fiber, plant-based diet on progression to myeloma. Although there are no data yet, the limited timeframes in these studies severely limits generalizability for outcomes that would truly matter, such as cancer control and longevity. There is also no evidence that changes in stool butyrate levels influence patient outcomes.

High-quality science — whether it is evaluating diet or other interventions—requires high-quality data, effort, funding, and time. It is not impossible.

We can draw inspiration from the CHALLENGE trial. This large, randomized trial, which took over a decade to complete, assessed the benefit of a structured exercise program in the adjuvant setting for colon cancer. The endpoint of this study was disease-free survival, and the intervention was deployed over a much longer period: 3 years, as opposed to a 2-week intervention. This trial took years from inception to completion, but it yielded a conclusive result and will probably lead to more dedicated efforts to facilitate exercise programs for patients with cancer.

Our patients deserve the same effort as the CHALLENGE trial to answer their important dietary questions. Until such trials are completed, we must acknowledge, with humility, that despite the common sense and feel-good factor that many diets offer us, their impact on cancer remains uncertain.

Conversely, we must recognize that even if diet does not cure or alter the course of a certain cancer, it can still impact quality of life, treatment tolerance, and other supportive care outcomes, making it an important factor in patient care.

This is what I tell my patients that it is unlikely any one diet will change the trajectory of your cancer. Focus on eating healthy, and remember that most things in moderation are fine. Your diet remains an important risk factor and determinant for health outcomes beyond cancer. Eat what makes you happy. You are going through a tough time, and this is not the moment to impose stringent restrictions on yourself.

A version of this article first appeared on Medscape.com.

The FDA has granted traditional approval to encorafenib (Braftovi, Pfizer) in combination with cetuximab (Erbitux, Eli Lilly) and fluorouracil-based chemotherapy for treatment of adults with metastatic colorectal cancer with a BRAF V600E mutation, as detected by an FDA-authorized test.

Encorafenib received accelerated approval for use with cetuximab plus mFOLFOX6 in this patient population in 2024, based on results from the BREAKWATER trial showing improved objective response rates. The conversion to full approval is supported by progression-free and overall survival outcomes.

As reported previously by Medscape Medical News, the combination of encorafenib/cetuximab/mFOLFOX6 doubled median overall survival compared with standard chemotherapy with or without bevacizumab. At a median follow-up of 22 months, overall survival was 30 months with the encorafenib regimen vs 15 months with standard chemotherapy (hazard ratio [HR], 0.49; P < .0001).

At median follow up of 16.8 months, median progression-free survival was 12.8 in the encorafenib group vs 7.1 months in the standard chemotherapy group (HR, 0.53; P < .0001).

The survival results are “unprecedented” and “practice changing” for these patients, who historically have a poor prognosis, lead investigator Elena Élez, MD, PhD, of Vall d’Hebron University Hospital in Barcelona, Spain, said in presenting the findings at the American Society of Clinical Oncology (ASCO) 2025 annual meeting.

The results were simultaneously published in The New England Journal of Medicine.

Speaking at the ASCO meeting, study discussant Andrea Sartore-Bianchi, MD, of the University of Milan, Italy, called the results “striking” and said the encorafenib combination should be considered the first-line standard of care.

As for safety, the rate of treatment-related grade 3/4 adverse events in the trial was 76% with encorafenib vs 59% with standard chemotherapy. Patients receiving encorafenib also had higher rates of anemia, arthralgia, rash, and pyrexia, but there was no substantial increase in treatment discontinuation.

The recommended encorafenib dose is 300 mg (four 75 mg capsules) once daily, in combination with cetuximab and mFOLFOX6 or in combination with cetuximab and FOLFIRI until disease progression or unacceptable toxicity, the FDA said in its approval announcement.

Prescribing information includes warnings and precautions for new primary malignancies (cutaneous and noncutaneous), tumor promotion in BRAF-wild-type tumors, cardiomyopathy, hepatotoxicity, hemorrhage, uveitis, QT prolongation, and embryo-fetal toxicity.

A version of this article first appeared on Medscape.com.

The FDA has granted traditional approval to encorafenib (Braftovi, Pfizer) in combination with cetuximab (Erbitux, Eli Lilly) and fluorouracil-based chemotherapy for treatment of adults with metastatic colorectal cancer with a BRAF V600E mutation, as detected by an FDA-authorized test.

Encorafenib received accelerated approval for use with cetuximab plus mFOLFOX6 in this patient population in 2024, based on results from the BREAKWATER trial showing improved objective response rates. The conversion to full approval is supported by progression-free and overall survival outcomes.

As reported previously by Medscape Medical News, the combination of encorafenib/cetuximab/mFOLFOX6 doubled median overall survival compared with standard chemotherapy with or without bevacizumab. At a median follow-up of 22 months, overall survival was 30 months with the encorafenib regimen vs 15 months with standard chemotherapy (hazard ratio [HR], 0.49; P < .0001).

At median follow up of 16.8 months, median progression-free survival was 12.8 in the encorafenib group vs 7.1 months in the standard chemotherapy group (HR, 0.53; P < .0001).

The survival results are “unprecedented” and “practice changing” for these patients, who historically have a poor prognosis, lead investigator Elena Élez, MD, PhD, of Vall d’Hebron University Hospital in Barcelona, Spain, said in presenting the findings at the American Society of Clinical Oncology (ASCO) 2025 annual meeting.

The results were simultaneously published in The New England Journal of Medicine.

Speaking at the ASCO meeting, study discussant Andrea Sartore-Bianchi, MD, of the University of Milan, Italy, called the results “striking” and said the encorafenib combination should be considered the first-line standard of care.

As for safety, the rate of treatment-related grade 3/4 adverse events in the trial was 76% with encorafenib vs 59% with standard chemotherapy. Patients receiving encorafenib also had higher rates of anemia, arthralgia, rash, and pyrexia, but there was no substantial increase in treatment discontinuation.

The recommended encorafenib dose is 300 mg (four 75 mg capsules) once daily, in combination with cetuximab and mFOLFOX6 or in combination with cetuximab and FOLFIRI until disease progression or unacceptable toxicity, the FDA said in its approval announcement.

Prescribing information includes warnings and precautions for new primary malignancies (cutaneous and noncutaneous), tumor promotion in BRAF-wild-type tumors, cardiomyopathy, hepatotoxicity, hemorrhage, uveitis, QT prolongation, and embryo-fetal toxicity.

A version of this article first appeared on Medscape.com.

The FDA has granted traditional approval to encorafenib (Braftovi, Pfizer) in combination with cetuximab (Erbitux, Eli Lilly) and fluorouracil-based chemotherapy for treatment of adults with metastatic colorectal cancer with a BRAF V600E mutation, as detected by an FDA-authorized test.

Encorafenib received accelerated approval for use with cetuximab plus mFOLFOX6 in this patient population in 2024, based on results from the BREAKWATER trial showing improved objective response rates. The conversion to full approval is supported by progression-free and overall survival outcomes.

As reported previously by Medscape Medical News, the combination of encorafenib/cetuximab/mFOLFOX6 doubled median overall survival compared with standard chemotherapy with or without bevacizumab. At a median follow-up of 22 months, overall survival was 30 months with the encorafenib regimen vs 15 months with standard chemotherapy (hazard ratio [HR], 0.49; P < .0001).

At median follow up of 16.8 months, median progression-free survival was 12.8 in the encorafenib group vs 7.1 months in the standard chemotherapy group (HR, 0.53; P < .0001).

The survival results are “unprecedented” and “practice changing” for these patients, who historically have a poor prognosis, lead investigator Elena Élez, MD, PhD, of Vall d’Hebron University Hospital in Barcelona, Spain, said in presenting the findings at the American Society of Clinical Oncology (ASCO) 2025 annual meeting.

The results were simultaneously published in The New England Journal of Medicine.

Speaking at the ASCO meeting, study discussant Andrea Sartore-Bianchi, MD, of the University of Milan, Italy, called the results “striking” and said the encorafenib combination should be considered the first-line standard of care.

As for safety, the rate of treatment-related grade 3/4 adverse events in the trial was 76% with encorafenib vs 59% with standard chemotherapy. Patients receiving encorafenib also had higher rates of anemia, arthralgia, rash, and pyrexia, but there was no substantial increase in treatment discontinuation.

The recommended encorafenib dose is 300 mg (four 75 mg capsules) once daily, in combination with cetuximab and mFOLFOX6 or in combination with cetuximab and FOLFIRI until disease progression or unacceptable toxicity, the FDA said in its approval announcement.

Prescribing information includes warnings and precautions for new primary malignancies (cutaneous and noncutaneous), tumor promotion in BRAF-wild-type tumors, cardiomyopathy, hepatotoxicity, hemorrhage, uveitis, QT prolongation, and embryo-fetal toxicity.

A version of this article first appeared on Medscape.com.

TOPLINE:

In patients with 5-20 brain metastases, stereotactic radiation improved symptoms and reduced interference with daily functioning compared to hippocampal-avoidance whole brain radiation. The weighted composite MD Anderson Symptom Inventory-Brain Tumor score changed from 2.69 to 2.37 with stereotactic radiation compared with 2.29 to 3.03 with hippocampal-avoidance whole brain radiation.

METHODOLOGY:

• Randomized trials have shown stereotactic radiation preserves neurocognitive function and patient-reported outcomes compared with whole brain radiation in patients with four or less brain metastases. For patients with more than four brain metastases, published randomized comparisons of stereotactic radiation vs whole brain radiation were lacking prior to this study.
• Researchers conducted a phase 3, open-label, randomized clinical trial at four US-based centers, enrolling 196 patients between April 2017 and May 2024, with final follow-up in March 2025.
• Participants included patients with 5-20 brain metastases and no prior brain-directed radiation, with a median of 14 brain metastases per patient and 25% having undergone prior neurosurgical resection.
• The primary outcome was the mean weighted patient-reported symptom severity and interference score change over 6 months. The researchers used the MD Anderson Symptom Inventory-Brain Tumor instrument, with scores ranging from 0-10 and change range of -10 to 10, to measure outcomes.
• Stereotactic radiation was delivered in either 1 day (20 Gy) or five daily fractions (30 Gy, or 25 Gy for surgically removed tumors), while hippocampal-avoidance whole brain radiation was administered as 30 Gy in 10 daily fractions with memantine.

TAKEAWAY:

• Primary outcome analysis showed that stereotactic radiation was linked to a change in the weighted composite MD Anderson Symptom Inventory-Brain Tumor score of 2.69 to 2.37 (mean change, -0.32) compared with 2.29 to 3.03 (mean change, 0.74) with hippocampal-avoidance whole brain radiation (mean difference, -1.06; 95% CI, -1.54 to -0.58; P < .001).
• Functional independence via the Barthel Index was better in the stereotactic radiation group at 4 months (mean difference, 6.79; 95% CI, 1.19-12.38; P = .02) and 12 months (mean difference, 7.92; 95% CI, 1.34-14.49; P = .02).
• New brain metastases were more frequent with stereotactic radiation (1-year cumulative incidence, 45.4% vs 24.2%; P = .003), while local recurrence was lower (3.2% vs 39.5%; P < .001).
• Grade 3-5 adverse events occurred in 12% of stereotactic radiation patients vs 13% in the hippocampal-avoidance whole brain radiation group, with fatigue being most common (28% vs 44%).

IN PRACTICE:

“While [the trial] clearly demonstrates that patients with 5-20 brain metastases have improved symptom burden and lowered interference with daily functioning, there are questions that remain for stereotactic radiosurgery in this population. Patients receiving stereotactic radiosurgery for brain metastases have a higher need for future salvage procedures, and this rate of salvage procedures is higher for patients with an increased number of brain metastases at diagnosis… Moreover, it has been shown that the upfront decision between stereotactic radiosurgery and whole brain radiotherapy is the single decision that contributes most to the cost of care of a patient with brain metastases,” said Michael Chan, MD, in an accompanying editorial published in JAMA.

SOURCE:

The study was led by Ayal A. Aizer, MD, MHS, Brigham and Women’s Hospital/Dana-Farber Cancer Institute, Boston. It was published online on February 19 in JAMA.

LIMITATIONS:

According to the authors, the study was not blinded, and the primary outcome was subjective. High mortality limited long-term data collection, reducing precision and biasing outcomes toward survivors. Additionally, randomization was not stratified by treating center, allowing possible unmeasured imbalances. The minimal clinically important difference had not been defined for many study outcome measures.

DISCLOSURES:

The trial was supported by Varian, a Siemens Healthineers Company. Aizer disclosed receiving grants from NH TherAguix Research outside the submitted work. Additional disclosures are noted in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

A version of this article first appeared on Medscape.com.

TOPLINE:

In patients with 5-20 brain metastases, stereotactic radiation improved symptoms and reduced interference with daily functioning compared to hippocampal-avoidance whole brain radiation. The weighted composite MD Anderson Symptom Inventory-Brain Tumor score changed from 2.69 to 2.37 with stereotactic radiation compared with 2.29 to 3.03 with hippocampal-avoidance whole brain radiation.

METHODOLOGY:

• Randomized trials have shown stereotactic radiation preserves neurocognitive function and patient-reported outcomes compared with whole brain radiation in patients with four or less brain metastases. For patients with more than four brain metastases, published randomized comparisons of stereotactic radiation vs whole brain radiation were lacking prior to this study.
• Researchers conducted a phase 3, open-label, randomized clinical trial at four US-based centers, enrolling 196 patients between April 2017 and May 2024, with final follow-up in March 2025.
• Participants included patients with 5-20 brain metastases and no prior brain-directed radiation, with a median of 14 brain metastases per patient and 25% having undergone prior neurosurgical resection.
• The primary outcome was the mean weighted patient-reported symptom severity and interference score change over 6 months. The researchers used the MD Anderson Symptom Inventory-Brain Tumor instrument, with scores ranging from 0-10 and change range of -10 to 10, to measure outcomes.
• Stereotactic radiation was delivered in either 1 day (20 Gy) or five daily fractions (30 Gy, or 25 Gy for surgically removed tumors), while hippocampal-avoidance whole brain radiation was administered as 30 Gy in 10 daily fractions with memantine.

TAKEAWAY:

• Primary outcome analysis showed that stereotactic radiation was linked to a change in the weighted composite MD Anderson Symptom Inventory-Brain Tumor score of 2.69 to 2.37 (mean change, -0.32) compared with 2.29 to 3.03 (mean change, 0.74) with hippocampal-avoidance whole brain radiation (mean difference, -1.06; 95% CI, -1.54 to -0.58; P < .001).
• Functional independence via the Barthel Index was better in the stereotactic radiation group at 4 months (mean difference, 6.79; 95% CI, 1.19-12.38; P = .02) and 12 months (mean difference, 7.92; 95% CI, 1.34-14.49; P = .02).
• New brain metastases were more frequent with stereotactic radiation (1-year cumulative incidence, 45.4% vs 24.2%; P = .003), while local recurrence was lower (3.2% vs 39.5%; P < .001).
• Grade 3-5 adverse events occurred in 12% of stereotactic radiation patients vs 13% in the hippocampal-avoidance whole brain radiation group, with fatigue being most common (28% vs 44%).

IN PRACTICE:

“While [the trial] clearly demonstrates that patients with 5-20 brain metastases have improved symptom burden and lowered interference with daily functioning, there are questions that remain for stereotactic radiosurgery in this population. Patients receiving stereotactic radiosurgery for brain metastases have a higher need for future salvage procedures, and this rate of salvage procedures is higher for patients with an increased number of brain metastases at diagnosis… Moreover, it has been shown that the upfront decision between stereotactic radiosurgery and whole brain radiotherapy is the single decision that contributes most to the cost of care of a patient with brain metastases,” said Michael Chan, MD, in an accompanying editorial published in JAMA.

SOURCE:

The study was led by Ayal A. Aizer, MD, MHS, Brigham and Women’s Hospital/Dana-Farber Cancer Institute, Boston. It was published online on February 19 in JAMA.

LIMITATIONS:

According to the authors, the study was not blinded, and the primary outcome was subjective. High mortality limited long-term data collection, reducing precision and biasing outcomes toward survivors. Additionally, randomization was not stratified by treating center, allowing possible unmeasured imbalances. The minimal clinically important difference had not been defined for many study outcome measures.

DISCLOSURES:

The trial was supported by Varian, a Siemens Healthineers Company. Aizer disclosed receiving grants from NH TherAguix Research outside the submitted work. Additional disclosures are noted in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

A version of this article first appeared on Medscape.com.

TOPLINE:

In patients with 5-20 brain metastases, stereotactic radiation improved symptoms and reduced interference with daily functioning compared to hippocampal-avoidance whole brain radiation. The weighted composite MD Anderson Symptom Inventory-Brain Tumor score changed from 2.69 to 2.37 with stereotactic radiation compared with 2.29 to 3.03 with hippocampal-avoidance whole brain radiation.

METHODOLOGY:

• Randomized trials have shown stereotactic radiation preserves neurocognitive function and patient-reported outcomes compared with whole brain radiation in patients with four or less brain metastases. For patients with more than four brain metastases, published randomized comparisons of stereotactic radiation vs whole brain radiation were lacking prior to this study.
• Researchers conducted a phase 3, open-label, randomized clinical trial at four US-based centers, enrolling 196 patients between April 2017 and May 2024, with final follow-up in March 2025.
• Participants included patients with 5-20 brain metastases and no prior brain-directed radiation, with a median of 14 brain metastases per patient and 25% having undergone prior neurosurgical resection.
• The primary outcome was the mean weighted patient-reported symptom severity and interference score change over 6 months. The researchers used the MD Anderson Symptom Inventory-Brain Tumor instrument, with scores ranging from 0-10 and change range of -10 to 10, to measure outcomes.
• Stereotactic radiation was delivered in either 1 day (20 Gy) or five daily fractions (30 Gy, or 25 Gy for surgically removed tumors), while hippocampal-avoidance whole brain radiation was administered as 30 Gy in 10 daily fractions with memantine.

TAKEAWAY:

• Primary outcome analysis showed that stereotactic radiation was linked to a change in the weighted composite MD Anderson Symptom Inventory-Brain Tumor score of 2.69 to 2.37 (mean change, -0.32) compared with 2.29 to 3.03 (mean change, 0.74) with hippocampal-avoidance whole brain radiation (mean difference, -1.06; 95% CI, -1.54 to -0.58; P < .001).
• Functional independence via the Barthel Index was better in the stereotactic radiation group at 4 months (mean difference, 6.79; 95% CI, 1.19-12.38; P = .02) and 12 months (mean difference, 7.92; 95% CI, 1.34-14.49; P = .02).
• New brain metastases were more frequent with stereotactic radiation (1-year cumulative incidence, 45.4% vs 24.2%; P = .003), while local recurrence was lower (3.2% vs 39.5%; P < .001).
• Grade 3-5 adverse events occurred in 12% of stereotactic radiation patients vs 13% in the hippocampal-avoidance whole brain radiation group, with fatigue being most common (28% vs 44%).

IN PRACTICE:

“While [the trial] clearly demonstrates that patients with 5-20 brain metastases have improved symptom burden and lowered interference with daily functioning, there are questions that remain for stereotactic radiosurgery in this population. Patients receiving stereotactic radiosurgery for brain metastases have a higher need for future salvage procedures, and this rate of salvage procedures is higher for patients with an increased number of brain metastases at diagnosis… Moreover, it has been shown that the upfront decision between stereotactic radiosurgery and whole brain radiotherapy is the single decision that contributes most to the cost of care of a patient with brain metastases,” said Michael Chan, MD, in an accompanying editorial published in JAMA.

SOURCE:

The study was led by Ayal A. Aizer, MD, MHS, Brigham and Women’s Hospital/Dana-Farber Cancer Institute, Boston. It was published online on February 19 in JAMA.

LIMITATIONS:

According to the authors, the study was not blinded, and the primary outcome was subjective. High mortality limited long-term data collection, reducing precision and biasing outcomes toward survivors. Additionally, randomization was not stratified by treating center, allowing possible unmeasured imbalances. The minimal clinically important difference had not been defined for many study outcome measures.

DISCLOSURES:

The trial was supported by Varian, a Siemens Healthineers Company. Aizer disclosed receiving grants from NH TherAguix Research outside the submitted work. Additional disclosures are noted in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

A version of this article first appeared on Medscape.com.

Transcript generated from video captions.

Hello. I'm Dr Maurie Markman, from City of Hope. I'd like to discuss over the next few minutes an absolutely provocative — and I don't use that term loosely — report that I would humbly suggest may, or perhaps even should, change standard of practice in the care of patients with breast cancer. The paper was published in the Journal of the National Cancer Institute, entitled, “Aprepitant Use During Chemotherapy and Association With Survival in Women With Early Breast Cancer.”

This is a very complex, important, and provocative topic, and I'm only going to have a short time to summarize these results, but again, I would suggest this is a topic worthy of very serious consideration in terms of the implications.

Aprepitant, as many of you know, is a standard antiemetic that has been used for many years. It’s very effective and very well tolerated. There’s not any question about that. It’s a supportive-care medication that may be used or not used; a variety of drugs might be used in its place.

However, there are preclinical data —I cannot go into any kind of detail here—that have revealed that aprepitant in these preclinical settings will slow breast cancer growth and progression.

What we're looking at in this report is retrospective data linking a nationwide registry of 13,811 women diagnosed with early breast cancer between 2008 and 2020 in Norway. These are population-based data that were very well documented because that's how things work in Scandinavian countries in general, but in Norway in particular. They know what patients receive nationally, over time, and there's follow-up.

The point is that they had knowledge of the diagnoses and the therapy. These women that I'm referring to had received chemotherapy and antiemetics, which, of course, is standard of care and has been for decades. These women were followed for the development of metastatic disease and death from 1 year after diagnosis to the end of 2021, which was the duration of this particular report.

During this period of time, of these 13,811 women, 7047 were given aprepitant, which is, interestingly, 51% or about half of the population. Here's the bottom line: Aprepitant use resulted in superior distant disease-free survival, with a hazard ratio of 0.89, and breast cancer-specific survival, with a hazard ratio of 0.83.

Increasingly interesting, only nonluminal breast cancer had this demonstrated benefit, with a hazard ratio of 0.69. Again, that's a hazard ratio for metastatic disease or death of 0.69 if aprepitant was used. It was strongest in triple-negative breast cancer, with a hazard ratio of 0.66. Let me repeat that: a hazard ratio of 0.66 for the reduction in the risk of distant disease or death. This was a difference that was able to be documented with the use of aprepitant or not.

Finally, in this analysis, survival outcomes were not observed with any other class of antiemetics, only aprepitant. In the nonluminal breast cancer population, the longer duration of aprepitant use — presumably multiple cycles over time — was associated with increasingly favorable survival outcomes. This was a trend analysis, so the longer it was used, the more superior the outcomes.

I’m not surprised. To get this paper published in a high-impact journal, the authors had to conclude that clinical trials are required to confirm these findings. Really?

If you're a patient, a family member, or an oncologist caring for a woman with triple-negative breast cancer, you are going to wait for a phase 3, randomized trial to be conducted and reported maybe in 5 or 10 years? When you're talking about a drug that is widely used and is safe, you're going to make a decision to wait for the clinical trial before you conclude that aprepitant should be used in this setting, based upon these excellent data?

I would challenge that and ask, on average today, certainly in patients that I'm seeing or counseling, aprepitant should become a component of the standard of care unless there's a contraindication to the use of the drug, based upon these excellent registry and population-based data.

We don't have to wait for randomized phase 3 trials to answer every question if what we see here makes sense, based on a plausible biological explanation and well-analyzed data. Obviously, other databases can look at this and see if they come up with different answers, but we do not need to wait for a phase 3, randomized trial before we incorporate something that we believe the data support as having a favorable impact on the outcome of patients we are seeing today.

I thank you for your attention.

A version of this article first appeared on Medscape.com.

Transcript generated from video captions.

Hello. I'm Dr Maurie Markman, from City of Hope. I'd like to discuss over the next few minutes an absolutely provocative — and I don't use that term loosely — report that I would humbly suggest may, or perhaps even should, change standard of practice in the care of patients with breast cancer. The paper was published in the Journal of the National Cancer Institute, entitled, “Aprepitant Use During Chemotherapy and Association With Survival in Women With Early Breast Cancer.”

This is a very complex, important, and provocative topic, and I'm only going to have a short time to summarize these results, but again, I would suggest this is a topic worthy of very serious consideration in terms of the implications.

Aprepitant, as many of you know, is a standard antiemetic that has been used for many years. It’s very effective and very well tolerated. There’s not any question about that. It’s a supportive-care medication that may be used or not used; a variety of drugs might be used in its place.

However, there are preclinical data —I cannot go into any kind of detail here—that have revealed that aprepitant in these preclinical settings will slow breast cancer growth and progression.

What we're looking at in this report is retrospective data linking a nationwide registry of 13,811 women diagnosed with early breast cancer between 2008 and 2020 in Norway. These are population-based data that were very well documented because that's how things work in Scandinavian countries in general, but in Norway in particular. They know what patients receive nationally, over time, and there's follow-up.

The point is that they had knowledge of the diagnoses and the therapy. These women that I'm referring to had received chemotherapy and antiemetics, which, of course, is standard of care and has been for decades. These women were followed for the development of metastatic disease and death from 1 year after diagnosis to the end of 2021, which was the duration of this particular report.

During this period of time, of these 13,811 women, 7047 were given aprepitant, which is, interestingly, 51% or about half of the population. Here's the bottom line: Aprepitant use resulted in superior distant disease-free survival, with a hazard ratio of 0.89, and breast cancer-specific survival, with a hazard ratio of 0.83.

Increasingly interesting, only nonluminal breast cancer had this demonstrated benefit, with a hazard ratio of 0.69. Again, that's a hazard ratio for metastatic disease or death of 0.69 if aprepitant was used. It was strongest in triple-negative breast cancer, with a hazard ratio of 0.66. Let me repeat that: a hazard ratio of 0.66 for the reduction in the risk of distant disease or death. This was a difference that was able to be documented with the use of aprepitant or not.

Finally, in this analysis, survival outcomes were not observed with any other class of antiemetics, only aprepitant. In the nonluminal breast cancer population, the longer duration of aprepitant use — presumably multiple cycles over time — was associated with increasingly favorable survival outcomes. This was a trend analysis, so the longer it was used, the more superior the outcomes.

I’m not surprised. To get this paper published in a high-impact journal, the authors had to conclude that clinical trials are required to confirm these findings. Really?

If you're a patient, a family member, or an oncologist caring for a woman with triple-negative breast cancer, you are going to wait for a phase 3, randomized trial to be conducted and reported maybe in 5 or 10 years? When you're talking about a drug that is widely used and is safe, you're going to make a decision to wait for the clinical trial before you conclude that aprepitant should be used in this setting, based upon these excellent data?

I would challenge that and ask, on average today, certainly in patients that I'm seeing or counseling, aprepitant should become a component of the standard of care unless there's a contraindication to the use of the drug, based upon these excellent registry and population-based data.

We don't have to wait for randomized phase 3 trials to answer every question if what we see here makes sense, based on a plausible biological explanation and well-analyzed data. Obviously, other databases can look at this and see if they come up with different answers, but we do not need to wait for a phase 3, randomized trial before we incorporate something that we believe the data support as having a favorable impact on the outcome of patients we are seeing today.

I thank you for your attention.

A version of this article first appeared on Medscape.com.

Transcript generated from video captions.

Hello. I'm Dr Maurie Markman, from City of Hope. I'd like to discuss over the next few minutes an absolutely provocative — and I don't use that term loosely — report that I would humbly suggest may, or perhaps even should, change standard of practice in the care of patients with breast cancer. The paper was published in the Journal of the National Cancer Institute, entitled, “Aprepitant Use During Chemotherapy and Association With Survival in Women With Early Breast Cancer.”

This is a very complex, important, and provocative topic, and I'm only going to have a short time to summarize these results, but again, I would suggest this is a topic worthy of very serious consideration in terms of the implications.

Aprepitant, as many of you know, is a standard antiemetic that has been used for many years. It’s very effective and very well tolerated. There’s not any question about that. It’s a supportive-care medication that may be used or not used; a variety of drugs might be used in its place.

However, there are preclinical data —I cannot go into any kind of detail here—that have revealed that aprepitant in these preclinical settings will slow breast cancer growth and progression.

What we're looking at in this report is retrospective data linking a nationwide registry of 13,811 women diagnosed with early breast cancer between 2008 and 2020 in Norway. These are population-based data that were very well documented because that's how things work in Scandinavian countries in general, but in Norway in particular. They know what patients receive nationally, over time, and there's follow-up.

The point is that they had knowledge of the diagnoses and the therapy. These women that I'm referring to had received chemotherapy and antiemetics, which, of course, is standard of care and has been for decades. These women were followed for the development of metastatic disease and death from 1 year after diagnosis to the end of 2021, which was the duration of this particular report.

During this period of time, of these 13,811 women, 7047 were given aprepitant, which is, interestingly, 51% or about half of the population. Here's the bottom line: Aprepitant use resulted in superior distant disease-free survival, with a hazard ratio of 0.89, and breast cancer-specific survival, with a hazard ratio of 0.83.

Increasingly interesting, only nonluminal breast cancer had this demonstrated benefit, with a hazard ratio of 0.69. Again, that's a hazard ratio for metastatic disease or death of 0.69 if aprepitant was used. It was strongest in triple-negative breast cancer, with a hazard ratio of 0.66. Let me repeat that: a hazard ratio of 0.66 for the reduction in the risk of distant disease or death. This was a difference that was able to be documented with the use of aprepitant or not.

Finally, in this analysis, survival outcomes were not observed with any other class of antiemetics, only aprepitant. In the nonluminal breast cancer population, the longer duration of aprepitant use — presumably multiple cycles over time — was associated with increasingly favorable survival outcomes. This was a trend analysis, so the longer it was used, the more superior the outcomes.

I’m not surprised. To get this paper published in a high-impact journal, the authors had to conclude that clinical trials are required to confirm these findings. Really?

If you're a patient, a family member, or an oncologist caring for a woman with triple-negative breast cancer, you are going to wait for a phase 3, randomized trial to be conducted and reported maybe in 5 or 10 years? When you're talking about a drug that is widely used and is safe, you're going to make a decision to wait for the clinical trial before you conclude that aprepitant should be used in this setting, based upon these excellent data?

I would challenge that and ask, on average today, certainly in patients that I'm seeing or counseling, aprepitant should become a component of the standard of care unless there's a contraindication to the use of the drug, based upon these excellent registry and population-based data.

We don't have to wait for randomized phase 3 trials to answer every question if what we see here makes sense, based on a plausible biological explanation and well-analyzed data. Obviously, other databases can look at this and see if they come up with different answers, but we do not need to wait for a phase 3, randomized trial before we incorporate something that we believe the data support as having a favorable impact on the outcome of patients we are seeing today.

I thank you for your attention.

A version of this article first appeared on Medscape.com.